Disorders of the hypothalamus and pituitary gland - Clin Med

What anterior pituitary hormone is the following

• Target Organ 

  • Mammary glands, ovaries

• Key Function

  • Milk production, estrogen/progesterone secretion

Prolactin (PRL)

What anterior pituitary hormone is the following

• Target Organ 

  • Liver, adipose tissue

• Key Function

  • Growth promotion

Growth Hormone (GH)

What anterior pituitary hormone is the following

• Target Organ 

  • Adrenal Gland

• Key Function

  • Secretion of glucocorticoids, mineralocorticoids, and sex corticoids

Adrenocorticotropic hormone (ACTH)

What anterior pituitary hormone is the following

• Target Organ 

  • Gonads

• Key Function

  • Sex-hormone production

Luteinizing hormone (LH)

What anterior pituitary hormone is the following

• Target Organ 

  • Gonads

• Key Function

  • Reproductive system growth (ovarian follicles growth, spermatogenesis)

Follicle-stimulating hormone (FSH)

What anterior pituitary hormone is the following

• Target Organ

  • Thyroid gland 

• Key Function

  • Secretion of thyroid hormone

Thyroid-stimulating hormone (TSH)

What posterior pituitary hormones is the following

Antidiuretic hormone (ADH; vasopressin)

What posterior pituitary hormone is the following (bottom one)

Oxytocin

What does this refer t

Hormone Axes and Effects

What does this refer to

• A 45-year-old woman presents to her primary care physician for persistent thirst.

• She has a past medical history of bipolar disorder and hypertension.

• She reports that the thirst began 4 weeks ago, along with increased trips to the bathroom.

• Her young cousin was recently diagnosed with diabetes after similar symptoms, and she is worried that she has diabetes.

• On physical exam, she has dry mucous membranes.

• A closer look at her medication list shows a new medication, lithium, started about 8 weeks ago.

Diabetes insipidus

What does this refer to

• Classified as central diabetes insipidus (CDI) or nephrogenic diabetes insipidus

• Absence of adequate ADH (decreased secretion or increased resistance) —> large volumes of very dilute urine

Diabetes Insipidus

What does this refer to

• History

  • Central diabetes insipidus (CDI): 50% have no known cause, during pregnancy have increased vasopressinase production

  • Nephrogenic DI: Usually result of increased ADH in collecting tubules

• Presentation

  • Polyuria and polydipsia are the hallmark symptoms, nocturia and thirst

  • In infants, watch for heavy/excessively wet diapers

Clinical history of Diabetes Insipidus

What does this refer to

• Dehydration

  • decreased weight

  • decreased skin turgor

  • increased capillary refill time

  • dry oral mucosa

  • orthostatic hypotension

  • tachycardia

• Mental status is usually unaffected

Physical examDiabetes Insipidus

What does this refer to

• Primary polydipsia

Differential diagnosis for Diabetes Inspidus

What does this refer to

WorkupDiabetes Insipidus

What does this refer to

• Aimed at reducing symptoms of polyuria, polydipsia, and nocturia

• CDI:

  • Desmopressin, typically taken before bed, is the preferred first-line treatment.

  • If excessive fluid intake continues, hyponatremia may result due to nonsuppressible ADH activity.

  • Serum sodium should be measured at 2 days after initiation and again at 4 days if normal.

  • Hydration

Clinical managementCentral Diabetes Insipidus

What does this refer to

• Based on patient’s symptoms

• Diet

  • low-sodium, low-protein diet in combination with NSAIDs and/or a thiazide diuretic.

• If cause can be attributed to medication use, a medication change should be considered.

• 1st line tx options

  • HCTZ

  • Indomethacin

  • Amiloride

    • Lithium induced

Clinical managementNephrogenic Diabetes Insipidus

What does this refer to

• A 25-year-old woman presents with her 4-day-old girl, born at full-term via spontaneous vaginal delivery complicated by postpartum hemorrhage, for a follow-up pediatric visit.

• She reports that she has not been breastfeeding, as her milk never “came in.”

• She has been feeding only with formula. (Sheehan syndrome)

Hypopituitarism

What does this refer to

• Decreased secretion of pituitary hormone(s)

• Universal decrease in function = panhypopituitarism

  • Sheehan syndrome: panhypopituitarism following postpartum hemorrhage

• MC causes: pituitary adenoma or surgical resection of a portion of the pituitary gland

Hypopituitarism

What does this refer to

• Given the relationship between the pituitary hormones and the function of the target organ

• Clinical presentation of hypopituitarism typically mimics the clinical presentation of a decrease in the target organ function

• Etiologies

  • Pituitary adenoma

  • Brain damage

  • Radiation therapy

  • Sheehan syndrome

History/PresentationHypopituitarism

What does this refer t

Hypopituitarism

What does this refer to

• Physical Examination

  • Highly varied based on hormone deficiency

Physical examHypopituitarism

What does this refer to

• Diagnostic Studies should be collected in the morning

  • Immunoassay of anterior pituitary hormones and their target hormones

    • Insulin-like growth factor

    • LH

    • FSH

    • Sex hormones (testosterone and estradiol)

    • TSH/free T4

    • Cortisol

    • ACTH

    • Prolactin

WorkupHypopituitarism

What does this refer t

Diagnostic Evaluation of Hypopituitarism

What does this refer to

• Varied based on individual hormones effected

  • Corticosteroids

  • Sex steroids

  • Growth hormone

  • Thyroxine

Clinical managementHypopituitarism

What does this refer to

• Pituitary infarct due to postpartum hemorrhage → hypovolemic shock

• Pregnancy causes increased pituitary size

  • Predisposes gland to hypoperfusion and ischemia

Sheehan Syndrome

What does this refer to

• Prolactin deficiency

  • Breast involution and failure to lactate

  • Amenorrhea

• Hypothyroidism

  • Cold intolerance

Clinical history/presentationSheehan Syndrome

What does this refer to

• MRI brain

  • Infarction of the pituitary gland

ImagingSheehan Syndrome

What does this refer to

• Hormone replacement therapy (HRT)

Clinical ManagementSheehan Syndrome

What does this refer to

• A 43-year-old man complains of increased hat size and headaches when he wakes up in the morning.

• Physical exam reveals mild hypertension, prominent jaw with spaces between the teeth, large hands and feet, and generalized muscle weakness.

Pituitary adenomas

What does this refer to

• Excessive growth after skeletal epiphyseal closure

• Due to ↑ growth hormone (GH)

Pituitary Adenoma

What does this refer to

• Rare

• Typically middle age at presentation

• F = M

• History

  • ~90% of sellar masses in adults >30 years old are pituitary adenomas

  • May have a delay between symptom onset and seeking care

  • All visual field defects should be worked up for sellar mass

EpidemiologyPituitary Adenoma

What does this refer to

• Not hereditary

• Many have spontaneous mutation leading to persistent ↑cyclic adenosine monophosphate (cAMP) in somatotroph cells

• Most are benign

EtiologyPituitary Adenoma

What does this refer to

• HA

• Sweating

• Clothes/hat fitting tight

• Amenorrhea or impotence

• Deep voice & slow speech

Clinical historyPituitary Adenoma

What does this refer to

• Diaphoresis

• Deep voice/slow speech

• HTN

• Mitral valve regurgitation

• Enlarged head with frontal bossing + deepened facial folds

• Enlarged jaw with increased teeth spacing

• Enlarged fingers and feet

• Skin tags

• Skin feels “doughy”

• Neuropathy

• Muscle weakness

Physical examPituitary adenoma

What does this refer to

• Gigantism

• Pseudoacromegaly

• Marfan syndrome

• Prolactinoma

Differential DiagnosisPituitary Adenoma

What does this refer t

WorkupPituitary Adenoma

What does this refer to

• Diagnostic studies (cont.)

  • If there is a primary disease (stemming from the target organ), the target organ hormone will be elevated but the stimulating hormone from the pituitary will be appropriately downregulated and appear low.

  • If there is secondary disease (stemming from the pituitary), both the target organ hormone and the pituitary stimulating hormone will remain elevated as the expected downregulation of the axis caused by excess circulating hormone is dysfunctional.

  • Hypothalamic releasing hormones can be used to distinguish tertiary disease from secondary disease.

WorkupPituitary Adenoma

What does this refer to

• Asymptomatic incidentalomas do not typically require treatment, but monitoring should be continued.

• Most pituitary adenomas require (surgical) transsphenoidal resection and is 1st line

  • resulting in hormonal insufficiency in approximately 7% to 20% of patients.

• Medical management

  • Somatostatin analog 1st line medical mgmt (inhibits GH production, ↓ tumor size prior to surgery)

    • Octreotide or Lanreotide)

  • Dopamine agonist 2nd line

    • Bromocriptine or Cabergoline

• Radiotherapy

  • Adjunct after resection

Clinical managementPituitary Adenoma

What does this refer t

PrognosisPituitary Adenoma

What does this refer to

• A 79-year-old woman is brought to the emergency department from home for altered mental status.

• Her family reports that she is normally alert and oriented to person, place, and time, and very conversational.

• On exam, she is confused, alert only to person, and appears anxious.

• She has moist mucous membranes and normal skin turgor.

• Pulmonary auscultation reveals localized crackles.

• Laboratory tests are significant for serum sodium of 126 mEq/L.

SIADH

What does this refer to

• Syndrome of Inappropriate ADH

• Excessive free water retention and impaired water excretion

• Results in dilutional hyponatremia

SIADH

What does this refer to

• Common in patients who are hospitalized

  • Esp. those on mechanical ventilation

• Risk Factors

  • Older age

  • Malignancy

  • Pulmonary disease

    • PNA

    • TB

EpidemiologySIADH

What does this refer t

EtiologySIADH

What does this refer to

• Na+ levels 125 – 130 mEq/L (mild)

  • Nausea

  • Malaise

• Na+ levels 115 – 125 mEq/L (moderate)

  • HA

  • Lethargy

  • Weakness

• Na+ levels < 115mEq/L (severe)

  • Seizures

  • Coma

  • Respiratory arrest

Clinical historySIADH

What does this refer to

• Euvolemia

  • No edema

  • Normal skin turgor

Physical examSIADH

What does this refer to

• Other causes of euvolemic hyponatremia

  • Hypothyroidism

  • Psychogenic polydipsia

  • Thiazide diuretic use

Differential diagnosisSIADH

What does this refer t

WorkupSIADH

What does this refer to

• Urine and serum osmolality are gold standard

  • Urine > serum

How’s it Diagnosed?SIADH

What does this refer t

Clinical managementSIADH

What does this refer t

Morbidity/mortalitySIADH

What does this refer to

Disorders of the Pituitary Gland