Endo/Heme/Onc Clinical Medicine Exam

Anterior pituitary hormones

• Growth hormone (GH): stimulate body growth

• Thyroid stimulating hormone (TSH): stimulates T3 and T4

• Prolactin (PRL): promotes lactation (milk production)

• Adrenocorticotropic hormone (ACTH): Release of glucocorticoids (cortisol)

• Follicle stimulating hormone (FSH): ovarian follicle maturation and sperm production

• Luteinizing hormone (LH): Ovulation and testosterone production

Posterior pituitary hormones

• ADH: signal kidneys to reabsorb more water into blood than excrete into urine

• Oxytocin: Stimulates smooth muscle contraction crucial for reproductive behavior and childbirth

Hypopituitarism

Anterior and Posterior

• S/S depends on which hormone is low

• All anterior pituitary hormones are low= panhypopituitarism

• Caused by: tumors, medical procedures, trauma, vascular issues, infections, AI conditions, congenital

Posterior hypopituitarism

Diabetes insipidus

Diabetes Insipidus pathophysiology

Inability to concentrate urine due to insufficient production of ADH (neurogenic/central) or insufficient renal response to ADH (nephrogenic)

• Central: pathology to hypothalamus, pituitary stalk, posterior pituitary

  • Primary: genetic/natural damage

  • Secondary: brain tumor, cranial surgery, aneurysms, thrombosis, infection

• Nephrogenic: End stage renal disease, drugs that affect renal tubules

Diabetes insipidus

• S/S: Intense thirst, large volume of water ingestion (2-20L a day), polyuria

  • If pt is unable to maintain their status they develop dehydration and hypernatremia

• Dx: 24 hour urine volume >2L, low urine osmolality, AVP levels (low in central form- measure of ADH)

  • MRI to check for central pathology

  • Vasopressin Challenge: administer desmopressin acetate intranasally

    • Measure urine volume, serum sodium before and after testing

      • Central DI: reduction of thirst and urine volume

      • Nephrogenic: no response

• Tx: Mild= none

  • Central: desmopressin acetate nasal spray Q12-24 hrs (NO STEROIDS)

Anterior Hypopituitarism

• Variable presentation based on affected hormones

• panhypopituitarism= all anterior pituitary hormones are low

• Types

  • Hypocortisolism: lack of ACTH

  • Hypothyroidism: lack of TSH

  • Gonadal failure and loss of secondary sex characteristics: lack of FSH/LH

  • Growth failure in children/ vague multi-syndrome in adults: lack of GH

• Non-specific S/S: fatigue, dizziness, HoTN, confusion

Growth hormone deficiency

• Risks

  • Congenital: newborns=failure to thrive, Laron syndrome (autosomal recessive, dwarfism)

  • Acquired: Radiation injury, compression, trauma

• S/S: Mild/Moderate: central obesity, decreased mental and physical energy, impaired concentration and memory, depression

  • Progressed: reduced muscle and bone mass, increased LDLs, reduced cardiac output

• Dx: Hard to measure d/t it being pulsatile, can measure blood sugar or insulin growth factor

Gonadotropin Insufficiency (hypogonadotropism)

• Hypogonadism and infertility (low levels of FSH and LH)

  • Congenital: partial or complete lack of pubertal development

  • Prader Willi: mental retardation, short stature, hyperphagia with obesity

  • Acquired: gradual loss of facial/axillary/pubic/body hair, diminished libido, infertility

• Dx

  • Men: low fasting/free serum testosterone

  • Women: low estradiol with normal or low FSH

TSH Deficiency

• Central hypothyroidism: fatigue, weakness, weight changes, hyperlipidemia, hyponatremia

• Dx: Low serum T4, low or normal TSH (low T4 should trigger production of more TSH)

ACTH Deficiency

Overlaps a lot with TSH deficiency, considered secondary hypoadrenalism

• S/S: Diminished cortisol- weakness, fatigue, weight loss, HoTN, hyponatremia

  • Partially diminished- may not manifest until stress or illness

• No S/S of mineralocorticoid deficiency (aldosterone secretion continues)

• Dx: Cosyntropin test

  • 8-9 a blood is drawn for serum cortisol (ACTH, DHEA), Cosyntropin 0.25 mg IV/IM is given

  • 45 mins later redraw (<20 mcg/dl= adrenal insufficiency, low baseline ACTH with low values of serum DHEA)

Prolactin Deficiency

Failure to lactate postpartum (puerperium)

Panhypopituitarism

• Congential: short stature, growth failure, GH/TSH deficiency, lack of pubertal development, low cortisol by 18

• Long-Standing: dry, pale, wrinkled facial skin with apathetic countenance (no emotion/interest)

General overview of Dx and Tx of Anterior hypopituitarism

• Dx

  • Initial: CBC and CMP (will likely demonstrate hyponatremia and hypoglycemia)

  • Perform individual specific tests per condition

  • Imaging: MRI in- men >16 with serum testosterone <150 mg/dL, HA/visual disturbances, 2+ pituitary hormone deficits)

    • NOT indicated in pts with functional hypopituitarism- severe obesity, drugs, nutritional disorders (all have dx causes)

• Tx: Lifelong hormone replacement therapy

  • Glucocorticoid (ACTH), Thyroid replacement (TSH), gonadotropin replacement (FHS/LH), hGH replacement (GH)

Difference between primary and secondary hypoadrenalism

• Primary: Addison’s dz- direct destruction of the adrenal glands

• Secondary: hypothalamus or pituitary failure to produce ACTH

Hyperpituitarism

• S/S depend on what hormones are being over secreted

• MCC is due to a functioning adenoma on the pituitary gland

  • Posterior: SIADH (syndrome of inappropriate ADH)

  • Anterior: Acromegaly/Gigantism and hyperprolactinemia

SIADH- Syndrome of Inappropriate Anti-Dieuretic Hormone

Excess ADH causing water retention, dilute blood (low sodium, hyponatremia)

• Risks: CNS (stroke, infection, trauma), Malignancy (tumor), drugs, sx, pulmonary disease, exogenous administration (desmopressin, vasopressin), HIV/infectious

• S/S: Serum hyponatremia, hpoosmolality, increased urine concentration which causes nausea, HA, confusion, fatigue, fluid overload

• Dx: (normal renal, adrenal, thyroid fxn)

  • Serum: hypoosmolality, hyponatremia

  • Urine: hyperosmolality, increased sodium excretion (not excreting as much= higher concentration)

• Tx: Identify and tx the underlying cause (ex. treat cancer)

  • Fluid restriction, correct hyponatremia (NOT rapidly)

  • Meds: Demeclocycline and Captains

Misleading causes for high growth hormone

• Exercise or eating before the test

• Acute illness or agitation

• Liver or kidney disease

• Malnourishment

• DM

Anterior hyperpituitarism

Excess secretion of anterior pituitary hormone, usually just one and others will be produces at lower levels

• Risks: pituitary adenoma, lack of feedback from the target gland (ex. no TH from the thyroid, increased production of TSH)

Acromegaly

excess growth of hands, feet, jaw, internal organs after puberty

• Thickening of nose and exacerbation of nasolabial folds

• Risks: nearly always a pituitary adenoma and secondary hypothyroidism can occur

Gigantism

GH increased before closure of the epiphyses (growth plate)- pre puberty

• Risks: sporadic, familial, can have ectopic cause (tumor, carcinoma)

Acromegaly/Gigantism

increased growth hormone that stimulates IGF-1 from liver and other tissues

• S/S

  • Gigantism: tall stature and gigantism in youth

  • Acromegaly: extreme enlargement; hands enlarge, facial features coarsen, macroglossia, weight gain, arthralgia, colon polyps, skin papilloma

• Dx: Serum IGF-1 initially (if normal acromegaly is r/o)

  • Fast and assy for: IGF-1, prolactin, glucose, liver enzymes/creatinine/BUN, serum free T4 and TSH, serum inorganic phosphorus

  • Glucose syrup oral and then serum GH measured 60 mins after- no acromegaly if <1ng/mL

  • Imaging: MRI (primary tumor in 90% of pts), radiographs can show bony enlargements

• Complications: hypopituitarism, cardiac enlargement/failure, carpal tunnel syndrome, arthritis, visual field deficits, colon polyps

• Tx

  • 1st: Transphenoidal pituitary microsurgery (monitor fluid, electrolytes, hyponatremia), give corticosteroids perioperatively (70% effective)

  • 2nd: MEDS: Cabergolin or Octreotide/Ianreotide (2nd/3rd line meds: Tamoxifen, Peguisomant)

    • For pts that cannot have sx or have incomplete recovery

  • 3rd: Stereotactic radio surgery- for pts that do not go into remission with 1st or 2nd line treatment→ lifelong ASA post-surgery

Hyperprolactinemia

Overproduction of prolactin usually caused by benign pituitary tumors (prolacinoma)

• Risks: prolactinoma

• S/S: Hypogonadotropic hypogonadism (high levels of prolactin suppresses GH-RH)

  • Men: diminished libido, ED that may not resound to tx, gynecomastia

  • Women: ammenorrhea, oligomennorhea, estrogen deficit (decreased vaginal lubrication, anxiety, depression), galactorrhea in absence of nursing

  • Large prolactinoma causes: HA, visual s/s, pituitary insufficiency

• Dx: R/O pregnancy (elevates prolactin levels), hypothyroidism, kidney dz, cirrhosis, hyperparathyroidism

  • Men: serum total and free testosterone, LH/FSH, PRL is measured on serial dilutions

  • Women: serum estradiol, LH/FSH, PRL is measured on serial dilutions

  • Imaging: Pituitary MRI

• Tx: Stop meds that induce, correct hypothyroidism, OCP for ammennorhea, pregnancy/infertility dopamine agonist

  • Dopamine agonists: Cabergoline, Bromocriptine

  • Sx: transphenoidal surgery or stereotactic radio surgery

    • Risks of: CSF leak, meningitis, stroke, visual loss

  • Chemo in a small number of patients

Adrenal hormones

• Aldosterone: sodium and water regulation in the body (Na and H20 reabsorb and K excrete)

• Androgens: Male sexual development, 2ndry sex characteristics, muscle and bone, libido, metabolism, estrogen in both sexes

• Cortisol: stress hormone, increases blood sugar levels, increases BP and decreases inflammation, plays a part of circadian rhythms (fluctuates)

• Catecholamines: epinephrine and norepinephrine

Adrenal disorders

• Primary adrenal insufficiency (Addison’s)

• Acute adrenal insufficiency

• Hypercortisolism (Cushing’s syndrome and disease)

• Hyperaldosteronism (Primary and Secondary)

• Pheochromocytoma

Primary Adrenal Insufficiency (Addison’s Disease)

AI due to failure of the adrenal gland

• Risks: Autoimmune (Hashimoto’s, celiac, T1DM), TB, HIV, metastatic cancer (lung, breast, GI), adrenal hemorrhage

• S/S: decreased aldosterone (hypotension, low Na, high K), low cortisol (hypoglycemia), low ACTH (no -FB)

  • Fatigue, arthralgia, N/V, anorexia, anxiety, salt cravings

  • Skin hyperpigmentation: ACTH stimulation can cause excess melanin production because they have the same precursor

Dx and Tx of Primary AI

• Dx

  • Labs: diluted blood osmolality (high ADH d/t low cortisol), hyponatremia and hyperkalemia (low aldosterone), hypoglycemia (low cortisol), low am (8 am or earlier) cortisol <7 ng/dL

  • ACTH (cosyntropin) stimulation test: 0.25 mg cosyntropin given IM and serum cortisol checked after 30 and 60 mins

    • Normal: serum cortisol doubles at 30 and 60 mins and should rise at least 20 mcg/dL

      • If normal check ACTH level

        • Primary: level is elevated because -FB is not happening

        • Secondary: ACTH and cortisol low because the pituitary gland is not stimulating the release

          • GET MRI

    • Adrenal insufficiency: little or no increase in cortisol levels (primary problem)

• Tx

  • 1st line: Hydrocortisone (titrated until good appetite and well-being)

  • ± 2nd line: Fludrocortisone (a lot of aldosterone problems: postural HoTN, decreased Na and increased K)

Pts with adrenal insufficiency or who are on chronic steroids that are having surgery need

Stress dose steroids

• IV solucortef 100 mg 1 hr prior to surgery

• IV 100 mg q8 hours x2 doses after surgery

Acute adrenal insufficiency

Emergency due to insufficient cortisol (significant adrenal collapse)

• Risks: abrupt cessation of chronic steroids, initial presentation of AI, stress to pts with underlying AI (trauma, surgery, extensive fasting, hyperthyroidism), adrenal surgery, pituitary necrosis

• S/S: HA, N/V, abdominal pain, fatigue, diarrhea, HoTN, hypoglycemia

  • Can progress to acute adrenal crisis: fever, shock, confusion, coma, death

• Tx: Hospitalization- IV normal saline (volume and hyponatremia) and IV hydrocortisone/dexamethasone

Hypercortisolism

• Cushing’s Syndrome: prolonged steroid use, ectopic ACTH secretion (SCLC tumor), adrenal tumor/hyperplasia

• Cushing’s Disease: pituitary adenoma producing ACTH

  • S/S: moon face, buffalo hump, protuberant abdomen, thin extremities, amenorrhea, ED, purple striae, easy bruisability, osteoporosis, HTN, poor wound healing

Dx and Tx of Hypercortisolism

Criteria (2/3 must be positive): lack of cortisol diurnal variation, reduced suppressibility of cortisol by dexamethasone, increased 24 hour urine free cortisol

1. Late night (11 pm) testing of salivary cortisol- normal <150, consistent above 250 are abnormal

2. Overnight dexamethasone suppression test: 1 mg given at 11 pm and cortisol tested next am- suppressed would be <1.8 mc/dL (-) test

3. 24 hour free urine cortisol level >50 mcg/day would be (+) test

• Distinguish ACTH dependent (pituitary) versus ACTH independent (Adrenal gland): measure ACTH and DHEAS

  • Pituitary gland: MRI

  • Adrenal gland: CT abdomen

  • Can’t find: CT abdomen and pelvis

• Tx: Surgical removal of tumor (pituitary or adrenal)

  • 2nd line (pts that cannot undergo surgery): Hypercortisol tx (Cabergoline, Pasireotide, Mifepristone), Ketoconazole, Metyrapone/Mitotane (SCLC)

Hyperaldosteronism

• Primary: excess aldosterone coming from adrenal glands themselves

  • Risks: idiopathic, adrenal hyperplasia, adrenal adenoma secreting aldosterone (Conn’s Syndrome)

• Secondary: Body has excess renin which causes adrenal glands to secrete more aldosterone

  • Risks: problem is coming from outside the adrenal gland (typically a kidney issue)

• S/S: suspect in patient with uncontrolled HTN with associated hypokalemia

• Dx: Hypokalemia with metabolic alkalosis (dumpling of K and H for Na)

  • Check PRA (plasma-renin activity)

  • ratio of aldosterone to PRA

    • Primary: decreased PRA and increased aldosterone

    • Secondary: increased PRA and aldosterone

• Tx: Aldactone (Spirnolactone) or Eplerenone (Tx BP and K levels)

  • Adrenal mass could mean sx

Pheochromocytoma

Catecholamine secreting adrenal tumor (epinephrine and norepinephrine)

• Risks: Rare, 90% benign, causes 2ndry hypertension

• S/S: palpitations, HA, excessive sweating

• Dx: elevated serum catecholamines, urinary metanephrines, chromogranin A

  • CT abdomen adrenal mass protocol

• Tx: BP meds, sx removal (control high BP prior to sx)

Goiters

Common in iodine deficient areas

• enlarged thyroid gland

Thyroid hormone serves to

• Increase basal metabolic rate

• increase heat production

• stimulate fight/flight

• increase heart rate

• stimulate growth

Causes of hypothyroidism

• Hashimoto’s

• Tx of hyperthyroidism

• Tx of thyroid cancer

• Iodine deficiency

• Toxins/drugs

• Congenital causes

Primary hypothyroidism (Hashimoto’s or surgical thyroidectomy)

Decreased secretion of T3 and T4 synthesis directly from the thyroid gland (increased TSH, decreased T3 and T4)

Hashimoto’s Thyroiditis (Primary autoimmune thyroiditis)

Autoimmune destruction of the thyroid gland by antithyroid antibodies leading to hypothyroid disorder (can have normal or high levels at first if hormones are being released d/t destruction)

• Risks: other AI diseases (Addison’s, hypoparathyroidism, DM, Sjogren’s, Vitiligo, pernicious anemia, biliary cirrhosis, celiac), women, 30-60 yo

• S/S: (usually symptoms of hypothyroid): fatigue, lethargy, dry skin, cold intolerance, constipation, depression, menorrhagia, voice hoarseness, carpal tunnel, Raynaud’s, deepening/hoarseness, periorybital eyelid edema, facial puffiness, bradycardia, weakness/cramping/stiffness, delayed relaxation of DTRs, inability to concentrate, myxedema madness, thinning of the lateral eyebrow, menorrhagia, menstrual irregularity, infertility, galactorrheamild, non-tender enlargement of the thyroid (high TSH)

• Dx: high TSH & low T3 and T4, +antithyroid peroxidase abys (anti-TPO), antithyroglobulin aby (anti-TG)

Secondary hypothyroidism

low secretion of TSH by the pituitary often part of panhypopituitarism (low TSH and low T3 and T4)

• Risks: pituitary malignancy, hemorrhage, surgery complication

Tertiary Hypothyroidism

deficiency of TRH released from the hypothalamus (low TRH, low TSH, low T3 and T4)

• S/S: cold intolerance, weight gain, constipation, fatigue, decreased sweating, HA, arthralgia, carpal tunnel, Raynaud’s, deepening/hoarseness, periorybital eyelid edema, facial puffiness, bradycardia, weakness/cramping/stiffness, delayed relaxation of DTRs, inability to concentrate, myxedema madness, thinning of the lateral eyebrow, menorrhagia, menstrual irregularity, infertility, galactorrhea

Diagnosis of hypothyroidism

• Labs: TSH, if TSH is normal then run T3/T4 (TSH with reflex), for primary run abys (anti-TPO, anti-TG)

• Subclinical hypothyroidism: high TSH with normal T3/T4, monitor d/t risk of overt hypothyroidism

• Other: hyponatremia, LDL(high)/triglycerides/liver enzymes, high serum creatine kinase, CBC (anemia)

Treatment of of hypothyroidism

Alleviate s/s and normalize TSH (caution that over correction can cause hyperthyroidism)

• 1st line: Levothyroxine (Synthroid, Levothyroid)- same time daily on an empty stomach (natural porcine options available as well)

• ± Liothyronine (Cytomel, Triostat)- adjunct therapy

• Takes 4-6 weeks for labs to change, 2 weeks for s/s to change

Complication of hypothyroidism- Myxedema Crisis

• rare and life threatening; MC d/t primary hypothyroidism and women that experience a stressful event, medications, or levothyroxine noncompliance

  • presents in pts with previously stable hypothyroidism

• S/S: AMS, hypothermia, hypoglycemia, hyponatermia, hypercapnia, hypoxia, bradycardia, seizures, hypoventilation, rhabdo

• Tx

  • Do first: ICU monitoring, mechanical ventilation, BP control (vasopressors, IVF), hypothermia correction (warming blankets), seizure control PRN

  • Then: Fluid management (hyponatremia, D5W), IV levothyroxine ± IV liothyrinone, glucocorticoid therapy, tx underlying conditions

Hyperthyroidism (thyrotoxicosis)- less common than hypothyroidism

Excess circulating thyroid hormone (T4 or T3) by the thyroid gland that is most common in females

• TSH suppressed in primary hyperthyroidism

• Primary Causes: Grave’s Disease (MC- diffuse toxic goiter), multi nodular toxic goiter (Plummer Dz, toxic thyroid adenoma

• Secondary causes: medications, pregnancy, transient hyperthyroidism (Hashimoto’s, subacute thyroid, postpartum), factitious, iodine induced, thyroid storm

• S/S: weight loss, polyphagia, frequent BMS/diarrhea, fine hand tremors, warm/moist skin and fever, sweating, brisk DTRs, hyperactivity/nervousness, anxiety/insomnia, palpitations, tachycardia, oligomenorrhea, amenorrhea, osteoporosis, onycholysis

Grave’s Disease- MCC of primary hyperthyroidism

Autoimmune disorder; autoimmune antibodies stimulate the TSH receptor (thyroid gland) to overproduce T3/T4

• Risks: older AI dz (Sjogren’s, celiac, pernicious anemia, Addison’s Dz, alopecia, T1DM, MG), female, 20-40 yo (can be triggered by a viral infection- COVID/COVID vaccine)

• S/S: diffuse toxic goiter, diffuse uptake on radioiodine scan

  • Infiltrative ophthalmology (Grave’s exophthalmos): bulging eyes, prominent stare, side lag

  • Infiltrative dermopathy (pretibial myxedema): fibroblasts on shins “peau d’orange”

  • Enlarged thymus, diffuse large non-tender thyroid ± thyroid bruit (ANA can be +)

Toxic multinodular goiter (Plummer’s disease)- 2nd MCC of primary hyperthyroidism

Autonomous hyper functioning nodules of the glands that produce high levels of T3/T4 and low TSH

• Risks: elderly, females, iodine deficient regions

• S/S: thyroid gland is bumpy, irregular and asymmetric (may also have symptoms of hyper)

• Dx: radioiodine uptake scan (patchy uptake- some hyper function and some atrophy)

Toxic Thyroid Adenoma- 3rd MCC of primary hyperthyroidism

Single nodule with otherwise atrophic gland (MC benign nodule of the thyroid)

• Dx: radioiodine uptake scan (uptake in the area of the adenoma)

• Tx: surgical removal of the toxic adenoma (curative)

Dx of hyperthyroidism

1. Elevation of free T4 & suppression of TSH

2. +Abys if Grave’s- thyroid stimulating immunoglobulins (TSI), thyrotropin receptor abys (TRAB)

• Anti-TPO and anti-TG can be positive in Grave’s (definitively present in Hashimoto’s)

3. Other: microcytic anemia, neutropenia, hypercalcemia, hypomagnesemia, increased LFTs

4. Subclinical hyperthyroidism: decreased TSH with normal T3/T4, occult risk of developing permanent

5. Imaging

• Thyroid ultrasound: patients with palpable nodules

• Radioactive iodine: test functioning of nodules (contraindicated in pregnancy and breastfeeding)

  • Hot: actively producing hormones and takes up more iodine

    • Grave’s= diffuse uptake

    • Toxic multi nodular/toxic adenoma= multiple focal patches of concentration

    • Thyroiditis= in area of adenoma

  • Cold: no uptake- concerning for malignancy

Tx of hyperthyroidism

• Initial relief: Beta-blocker

• Hormone control: Methimazole (preferred) or propyithiouracil (PTU, used in pregnancy and family planning)- can cause agranulocytosis/pancytopenia and used as a pretreatment of sx

• Curative Treatment: Radiation (radioactive iodine) or surgery

1. Radioactive Iodine: destroy thyroid tissue and is indicated in patients 60+ or those with comorbidities to surgery, methiamazole to pretreat and avoid hyperthyroidism (can worsen Grave’s ophthalmology: presence is a relative contraindication and pre-treat with prednisone)

2. Surgery (thyroidectomy): most definitive treatment and indicated in patients that fail meds, have a large compressing goiter, contraindication to RAI (grave’s= total thyroidectomy, partial thyroidectomy= toxic multi goiter and isolated hot nodules)

Complication of hyperthyroidism- Thyroid Storm

One or more mechanisms to metabolic stress of hyperthyroidism is decompensated

• Risks: pts with untreated hyperthyroidism or during/post significant stress: sx, infection, illness

• S/S: rapid superventricular arrhythmias, CHF, hyperpyrexia, AMS, sweating

• Tx: ICU, IV fluids, O2, cardiac monitoring

  • B-blocker (propranolol), PTU(Better)/Methimazole ± ipodate sodium, glucocorticoids, iodine solution

Complication of hyperthyroidism- Thyroid Eye Dz

exophthalmos d/t deposition of mucopolysaccharides and infiltration with chronic inflammatory cells in orbital tissues and extra ocular mm.

• S/S: lid lag, chemosis, dry eye, episcleral inflammation, fixed stare, bulging, loss of visual acuity

• Tx: refer ophthalmology (supportive and Teprotumumab)

Hyperthryroidism in the elderly can look like

depressed, cachectic, anorexia, constipation, apathetic

• appears differently

Thyroiditis

Inflammation of thyroid gland leading to damage of the cells that produce TH

• Initially hyperthyroidism (trigger release of all that is left)→ hypothyroidism (damaged, no T3/T4)

• range of s/s (usually hypothyroid at time of presentation)

• Causes: Hasimoto, postpartum, painful subacute (deQuervian’s), infectious (supperative), Ig-G4-related (Riedel’s)

  • Others: Medications (amiodarone, immunomodulators), MEN, APS

Postpartum thyroiditis

• inflammation after delivery that causes transient hyperthyroidism (release of stored hormones) then hypothyroidism (increased antithyroid antibodies)

• Risks: Pregnancy/childbirth, MC with a family or personal history of thyroid/endocrine dz

• Tx: May or mat not treat, use propranolol

• Painless

Subacute thyroiditis (Subacute granulomatous thyroiditis, de Quervains)

Self limited thyroid inflammation of viral origin

• Risks: URI, COVID

• S/S: pain in anterior neck that radiates to the jaw, ear, chest, and have pain an difficulty swallowing

  • moderately enlarged, asymmetrical, exquisitely tender to palpation (TTP)

• Dx: variable thyroid abnormals, leukocytosis, increased ESR/CRP

• Tx: not needed

  • 1st line: NSAIDs/ASA ± Beta blockers (if NSAID/ASA not enough can use prednisone)

IgG4 related (Riedel’s) Thyroiditis

Fibrotic invasion of the thyroid

• Risks: elderly/middle aged women

• S/S: painless, asymmetric thyroid enlargement, stony (adherent to near structure)

• Tx: Tamifoxen, Sx if compressing on structures

Infectious (suppurative) thyroiditis

Non-viral infection of the thyroid

• Risks: immunosuppressed patients

• S/S: fever, severe pain, redness, fluctuation, warm to touch, tender

• Labs: increased ESR, leukocytosis

• Tx: Abx ± surgical drainage (may need thyroidectomy)

Thyroid nodule Dx and workup

• Workup: initial hx, PE, U/S, TSH levles

• PE: fixed nodules with rapid growth and hoarseness is worrisome for cancer

  • Recurrent laryngeal nerve damage= hoarseness and paralysis of vocal cords

• Labs: TSH, FT4/FT3 ± calcitonin levels (medullary thyroid carcinoma)

• Imaging

1. Thyroid U/S: shape and size of nodule (calcification, irregular borders, invasion into tissue)

2. RAIU: supplemental role, evaluate for hyperthyroidism

3. FNA: 95% sensitive and specific for all cancers besides follicular→ can f/u with open bx

Papillary thyroid cancer

80% of thyroid cancer (MC), usually a single nodule that is slow growing and rarely metastasizes (would to a regional lymph node)

• Tx: Sx ± RAI ablation (concentrates iodine so can use RAI)

Follicular thyroid cancer

2nd MCC of thyroid cancer, metastasize to the neck/bone/lung; can secrete hormone and produce thyrotoxicosis (serum thyroglobulin levels elevate)

• Tx: RAI ablation therapy (concentrates iodine so can use RAI)

Medullary thyroid cancer

2-3% of thyroid cancer cases 3rd MCC, metastasize early and arise from parafollicular cells (secrete calcitonin (watch for carcinoid syndrome), prostaglandins, serotonin, ACTH)

• Risks: genetics/family, MEN 2 and 3

• Tx: Sx and chemo (does not concentrate iodine)

Anaplastic Thyroid Cancer

4th MCC of thyroid cancer, older patient with rapidly enlarging mass in a multi nodular goiter

• most aggressive thyroid canes with early and distant metastasis

• Tx: Sx and chemo (does not concentrate iodine)

Thyroid nodule treatment

• 1st line: Always treat with surgery

  • Total thyroidectomy: first line for all aggressive types

  • Lobectomy: cancers 1cm>cancer<4cm

  • Complications: hypothyroidism, hypoparathyroidism, recurrent laryngeal nerve injury

• ± Radioactive iodine ablation (papillary or follicular)

• Thyroxine slows tumor growth

• Monitor: thyroglobulin (papillary and follicular), calcitonin (medullary)

Endemic goiter

Multinodular and large goiter d/t iodine deficiency

• Risks: regions with a low iodine diet (low risk of malignancy)

• Tx: most are euthyroid, iodine supplementation, Sx removal only if compressive

Causes of hypoparathyroidism

1. Acquired: MCC by neck surgery, all patients undergoing thyroidectomy/parathyroidectomy/ radiation should be followed

2. Autoimmune: isolated AI dz or associated with other AI dz, can be Lupus related

3. Other: heavy metal toxicity, magnesium deficiency, congenital

Function of the parathyroid gland is to

Control Ca++ levels

• works with vitamin D to increase serum calcium concentration

• PTH acts on bone and kidney

• Ca++ is albumin bound- order ionized Ca (free and active) or correct for serum albumin

S/S of hypoparathyroidism

Many are asymptomatic or have s/s of hypocalcemia

• Neuromuscular irritability: carpopedal spasm, tingling of lips/hands/muscles, abdominal cramps, psych changes, tetany

• PE: + Chvosteks (facial nerve spasm with tapping of the nerve), +Trousseaus (carpal spasm with arterial occlusion), defective hair/skin/nails, possible seizures, bradycardia/ventricular arrhythmias and decreased EF, prolonged QT intervals

Dx and Tx of hypoparathyroidism

• Dx: hypocalcemia, decreased PTH, increased serum phosphate

  • serum calcium low, serum phosphate high (no PTH= no phosphate excretion), alkalinity phos normal, urine Ca+ can be high serum magnesium low

• Tx

  • Severe/tetany: airway maintenance, IV calcium gluconate (switch to PO when able), when PO for Ca start PO Vit D, Magnesium if deficient

  • Maintenance (if having symptoms or Ca+ is <8.0 mg/dL):

    • 1st line: PO Calcium, vitamin D PO (monitor serum calcium every 3 months or less)

    • 2nd: Palopegteriparatide (Yorvipath) and Teriparatide (Forteo)

Causes of hyperparathyroidism

1. Primary: functional single parathyroid adenoma or hyperplasia of 2+ glands/ectopic parathyroid glands (associated with MEN)

2. Secondary: chronic renal dz (increased phosphate binds Ca+, increased stim of PTH)

• Risks: causes hypercalcemia/hypercalciuria, 70’s, women

S/S of hyperparathyroidism

Asymptomatic or s/s will relate to hypercalcemia- “Bones, stones, abdominal groans, psychic moans with fatigue”

• Bone pain, renal stones, constipation, polyuria, mental changes (HA, insomnia, irritability depression), fatigue, muscle weakness/parasthesia

• EKG: prolonged PR interval, shortened QT interval

Dx and Tx of Hyperparathyroidism

• Dx: Hypercalcemia (>10.5 mg/dL), increased serum PTH, decreased serum phosphate

  • can measure 24 hour urine calcium (borderline or high)

  • imaging to look for ectopic glands/hyperplasia (U/S, CT, MRI)

  • Consider DEXA (osteoclast activity- osteopenia/osteoporosis)

• Tx

  • 1st line: Surgical parathyroidectomy

  • Med management: large fluid intake

    • Calcimimetics (Cinacalcet-PO): bind to receptor sites in parathyroid and block PTH production

    • Bisphosphonate: calm bone pain

    • Vitamin D replacement to decreased PTH levels

    • NO THIAZIDE DIEURETICS OR DIETARY CALCIUM

Causes of hypocalcemia

• Hypoalbumenemia

• Malabsorption of Ca+, Vit D, Mag

• Acute pancreatitis

• Meds: loop dieuretics, phenytoin, Foscarnet (antiviral)

Causes of hypercalcemia

• Malignancy

• adrenal insufficiency

• chronic renal failure

DM autoantibody panel- present in Type 1 DM

• Islet cell autoaby (ICAs)

• Autoaby to insulin (IAAs)

• Autoabys to glutamic acid (GAD65)

• Autoabys to zinc transport 8 (ZnT8)

Diabetes Mellitus

Metabolic disorders characterized by failure of feedback system to regulate blood and glucose levels

Types of Diabetes

1. Type 1 DM: AI condition where immune system attacks and destroys pancreatic islet beta cells→ endogenous insulin deficiency and hyperglycemia (ABYS PRESENT)

2. Type 2 DM: Insulin resistance of peripheral cells in muscles, tissues, fat; inadequate insulin production by the pancreas and increased production of glucose by the liver

3. Gestational dibetes: hyperglycemia developing during pregnancy, typically resolving after birth

4. Monogenic Diabetes syndrome: characterized by mutations in a single gene, including neonatal diabetes and mautiry onset diabetes of the young (MODN)- EARLY T2

5. Pancreatic Dz: (pancreatitis, cystic fibrosis, CA) causing diabetes and pancreatic damage

6. Drug-Induced: hyperglycemia caused by medications (glucocorticoids, TH, beta blockers)

7. Latent Autoimmune Diabetes in adults (LADA): subtype of T1DM that involves AI attack on pancreas occurring later on in life after the age of 30 (MC + for GAD65 aby)

Risks of diabetes

• T1DM: children 4-6/10-14, weak genetic link, other AI conditions, environmental triggers high incidence further from equator (like MS)

• T2DM: overweight/obese, sedentary lifestyle, strong genetic component, ethnicity (AA, hispanic, asian American, Pacific Islander, native american), gestational diabetes hx, PCOS, metabolic syndrome

• Gestational: pregnancy, AA/hispanic/american Indians, obese women (ALWAYS tx with insulin)

• Secondary: consequence of medical conditions or medications

  • Conditions: endocrine tumor, acromegaly, Cushing syndrome, pheochromocytoma, thyrotoxicosis, chronic pancreatitis

  • Meds: glucocorticoids, atypical antipsychotics, B-blockers, CCB, niacin, protease inhibits, thiazide diuretics

S/S of DM

• All: polydipsia/polyuria/polyphagia, unexplained weight loss (T1), fatigue, blurred vision, slow healing sores, frequent infection

• T1: suddenly, children/teens/young, ketoacidosis (DKA), weight loss

• T2: gradual, >45 yo, ancanthosis nigricans (velvet crease/discoloration)

Dx of DM

• Screening: T2DM at 45 yo in all pts, sooner if overweight or have risk factors (fasting glucose)

• Abnormal tests of glycemia (1+ with symptoms, 2+ w/o symptoms)

  • Fasting blood glucose >126 (8 hr fasting)

  • 2-h blood sugar after 75g oral glucose tolerance test (OGTT) >200

  • Hemoglobin A1C >6.5%

  • Random blood sugar > 200 with symptoms

• ± Aby testing (T1DM), mc Islet abys positive (ICAs)

• ± C-peptide testing: almost undetectable in T1DM

• Ketones: urinary/blood samples, Dx DKA in T1DM (>0.6= eval, >3= hospitalization)

Hgb A1C

• Normal: 5.7%>

• Prediabetic: 5.7%-6.4%

• Diabetic: >6.5%

  • DM goal <7%

  • Kidney failure= false elevation

  • Liver disease= false decrease

  • Does not factor in RBC dz

Prediabetes

Blood sugar higher than normal but does not meet criteria for dx of diabetes

• warning to make a lifestyle change

• Prevention of progression: lifestyle change, weight loss, physical activity, glucose monitoring, Metformin, medication, regular visits, smoking cessation

• Criteria

  • HBA1C: 5.7-6.4%

  • Fasting glucose: 100-125 mg/dL

  • Oral GGT: 140-199 mg/dL

  • Random plasma glucose: 140-199 mg/dL

Insulin resistance syndrome (metabolic syndrome)

Conditions that increase risk of heart disease, stroke, T2DM

• 3 or more of the following:

  • increased blood sugar

  • HTN

  • excess body fat around the waist

  • low HDL

  • high triglycerides

  • prothromotic state

  • proinflammatory state

  • insulin resistance

Initial tx of T2DM

1. Healthy lifestyle change (diet/exercise) with a focus on weight loss, consult diabetic educator/nutritionist

2. Medication therapy

Stepwise management of T2DM

1. At dx= weight loss, exercise, Metformin

2. If HBA1C not at target (<7%) after 3 months= Metformin+ another agent

3. If HBA1C not at target (<7%) after 3 months= Metformin+ 2 other agents

4. If HBA1C not at target (<7%) after 3 months=Metformin+insulin± another agent

Diabetes Meds to use in special cases

• Good for CV: Metformin, liraglutide, semaglutide, empagliflozin, canagliflozin

• Good for Renal: Flozins (SGLT2-I)

• Cause hypoglycemia: secretagogoues, insulin

• Good for weight loss: GLP-1, SGLT2-I

Management of T1DM

• 4 measurements of blood glucose daily (3-4 insulin injections daily), combo of rapid and long lasting insulins

• Ex

  • Pre breakfast: 5 units rapid, 6-7 of insulin detemir

  • Pre lunch: 4 units rapid

  • Pre-dinner: 6 units rapid

  • Bedtime: 8-9 units of insulin detemir

Changing from another insulin regimen to basal/bolus regimen insulin

Total daily dose (70-75% of prior)

• 50% basal

• 50% bolus (usually divided into 3 pre-meal doses)

Hypoglycemia

Blood glucose around 60 activates parasympathetic (nausea/hunger) and sympathetic (tachycardia/palpitations/sweating) nervous systems and can progress to confusion and coma

• all pts on insulin or secretagogues should carry glucose tablets or juice and be prescribed a parenteral glucagon emergency kit

• take blood sugar when feel initial s/s (beta blockers can hide s/s of the sympathetic nervous system) and then again in 15 minutes after dosing

• unconscious give glucagon sq or IM

Complications of diabetes

• Acute: DKA (T1), HHS (T2), somogyi effect, dawn phenomenon, hypoglycemia

• Chronic: multiple conditions that affect many body systems d/t pathological change in small and large vessels (leads to HTN, MI, ESRD, blindness, neuropathy, amputations, CVA)

Diabetic ketoacidosis (short term diabetes complication)- Life threatening

Blood glucose rises rapidly d/t gluconeogenesis and progressive increase of fate breakdown; get polyuria and dehydration and increased ketone levels bc of fatty acids that are being used for energy

• Risks: T1DM (can occasionally be the presenting symptom), physical stress (pregnancy, acute illness, trauma)

• S/S: “fruity” breath, Kussmaul’s respirations (deep, rapid, strenuous breathing), metabolic acidosis pH<7.3, ketonuria, N/V, dehydration, low potassium

• Dx: urinalysis, CMP, CBC

• Tx: SIPS- saline, insulin, potassium, search for a cause

Hyperosmolar hyperglycemia nonketoic coma (HHS)- aka hyperosmolar hyperglycemic state (short term diabetes complication)

Insulin deficiency, drastic worsening of T2DM that is not-ketosis prone and the plasma osmolality is >310 mOsm/L

• Risks: T2DM

• S/S: loss of liters of urine, massive thirst, severe potassium deficit

• Tx: SIPS- saline, insulin, potassium, search for a cause

Somogyi Effect

Deep decrease in blood glucose levels (trigger a reflex in glucagon, catecholamines, GH, cortisol) during the night followed by a rebound increase in the morning

• Risks: inappropriate evening insulin dose, MC in children

• Tx: adjust evening insulin to stop hypoglycemia, dietary change like an evening snack

Dawn Phenomenon

Early morning (5-9am) hyperglycemia d/t circadian increase in glucose levels in the morning (cortisol and GH naturally surge in the morning)

• Risks: T1 and T2 DM

• Tx: bedtime injection of NPH (long acting insulin) or increase bedtime does of insulin and avoid carbs at night

Ocular complications of diabetes

Need annual consult with ophthalmology, leading cause of blindness in the U.S.

• Cataracts: premature cataracts and directly correlate with severity of the dz

• Glaucoma: MC in pts with diabetes after cataract extraction sx, neovasc→AACG

• Retinopathy: damage to the retina d/t lack of O2, breakdown of capillary structure, microaneurysm, spots of hemorrhage

  • Non proliferative: earliest stage, micro aneurysm/dot hemorrhage/exudate/retinal hemorrhage (>60% of T2DM after 16 years)

  • Proliferative (MC in T1DM): growth of new vessel and fibrous tissues in the retina and predispose to vitreous hemorrhage and retinal detachment

Renal complications of diabetes

Damage to glomerular capillaries d/t HTN and increased plasma glucose (worse in DM+HTM combo)

• nodules, protein in urine, generalized edema, tissue hypoxia fluid overload, HTN, metabolic acidosis, bone breakdown, RBC deficiency/anemia, decreased glomerular filtration

• Tx: ACE/ARB (HTN and renal protective), yearly albumin/creatinine ratio

Cardiovascular complications of diabetes

Micro/macro vascular damage and organ damage (give DM patients prophylactic Aspirin)

• Microvascular: thickening of vessels, ischemia, decreased O2 and nutrients in tissues

• Macrovascular: poor blood flow (atherosclerosis)

• CAD (high risk of morbidity and mortality), stroke, PVD

Neuropathic complications of diabetes

Damage to sensory/motor cause by hypoxia and effects of hyperglycemia

• Peripheral neuropathy: symmetric, stocking-glove (sensory changes→ dull vibration, pain, and temperature)

  • decreased sensation can continue to diabetic foot ulcers

• Autonomic: gatroparesis, N/V, constipation/diarrhea, orthostatic HoTN, ED

Skin complications of diabetes

• Candidal infections (especially type 2), eruptive cutaneous xanthomas (lipid abnormalities)

• Necrobiosis lipoidica diabeticorum: well demarcated waxy yellow atrophic plaque→ use topical steroids

• Diabetic shin spots: brown, round atrophic lesions (painless) in pretibial area

MSK complications of diabetes

• Joint arthropathy, adhesive capsulitis, carpal tunnel syndrome, Duputren’s contracture, gout, bursitis

• decreased bone density and high rates of fractures

• Charcot foot

MEN- Multiple Endocrine Neoplasia

Autosomal dominant gremlin mutation→ predisposes patient to a tumor

• Men 1: 3 P’s: parathyroid, pancreas, pituitary, mutation in menin gene, may 1st present as hyperparathyroidism

• Men 2: Medullary thyroid CA, hyperparathyroidism, pheochromocytoma, Hirschprung Dz, d/t RET gene (no GLP-1)

• Men 3: mucosal neuromas, Marfan-like habits, d/t RET protooncogene (no GLP-1)

• Men 4: tumors of ovaries, testicles, kidneys, d/t CDKN1B gene

  • S/S: variable d/t location of tumor; hypercalcemia, hyperparathyroidism

  • Dx: genetic testing

  • Tx: partial or total excision of glands