[05.07] CMD - Hypothalamic-Pituitary Gland Disorders V2.1.pdf

GHRH (+), Somatostatin (-), TRH (+), CRH (+), GnRH (+), Dopamine (-)

Which hypothalamic hormones stimulate or inhibit anterior pituitary hormones?

Insulin-like growth factor-1 (IGF-1)

What is the primary target mediator produced by the liver in response to Growth Hormone?

Thyroxine (T4) and Triiodothyronine (T3)

What primary target gland hormones are secreted by the thyroid in response to TSH?

Cortisol

What primary steroid hormone is secreted by the adrenal cortex in response to ACTH?

Estrogen, progesterone, and testosterone

What sex steroids are secreted by the gonads in response to FSH and LH?

Dopamine

Which hypothalamic neurotransmitter tonically inhibits prolactin secretion from the anterior pituitary?

Hypothalamus

Where are the posterior pituitary hormones oxytocin and vasopressin synthesized?

Uterine contraction and milk letdown

What are the primary physiological roles of oxytocin?

Renal tubule water reabsorption and osmotic pressure regulation

What is the primary physiological role of Antidiuretic Hormone (ADH)?

Primary Endocrine Disorder

What category of endocrine disorder involves pathology within the target organ itself, with the pituitary and hypothalamus responding appropriately?

Secondary Endocrine Disorder

What category of endocrine disorder stems from pathology in the pituitary gland affecting the target organ?

Suppression Tests

What type of confirmatory diagnostic test is indicated when a patient is suspected of having hormone excess?

Stimulation Tests

What type of confirmatory diagnostic test is indicated when a patient is suspected of having hormone deficiency?

Hormonal excess, hormonal deficiency, and mass effect

What three primary mechanisms cause clinical manifestations in patients with hypothalamic-pituitary disorders?

Hypogonadism, hypothyroidism, growth failure, hypoadrenalism, and hyperprolactinemia

What endocrine deficits result from direct pituitary compression by a sellar mass?

Stalk compression blocking hypothalamic dopamine from reaching the anterior pituitary

By what mechanism does a sellar mass cause hyperprolactinemia without a prolactinoma?

Bitemporal hemianopia

What classic visual field defect is caused by a sellar mass expanding superiorly to compress the optic chiasm?

Loss of red perception

What early color vision deficit can indicate optic chiasm compression by a pituitary lesion?

Temperature dysregulation, appetite/thirst disorders, obesity, AVP deficiency, sleep, and behavioral disorders

What clinical features occur when a sellar mass extends to impact the hypothalamus?

Ophthalmoplegia, ptosis, diplopia, and facial numbness

What neuro-ophthalmologic signs result from lateral extension of a sellar mass into the cavernous sinus?

Cranial Nerves III, IV, V1, V2, and VI

Which cranial nerves traverse the cavernous sinus and can be compromised by an expanding sellar lesion?

Personality disorder and anosmia

What clinical manifestations occur if a sellar mass extends anteriorly to involve the frontal lobe and olfactory bulb?

Headache, hydrocephalus, psychosis, dementia, and laughing seizures

What brain complications can arise from massive suprasellar mass extension?

Circadian rhythm

What physiological variance requires timing hormone blood draws at specific hours (e.g. morning vs. midnight)?

Serum IGF-1

What is the initial screening blood test of choice for suspected acromegaly?

Failure of GH to suppress to < 1.0 mcg/L (or < 0.4 mcg/L) after an oral 75g glucose load

What result on an Oral Glucose Tolerance Test confirms the diagnosis of acromegaly?

Basal fasting morning serum prolactin level

What initial screening test is ordered for a suspected prolactinoma?

24-hour urine free cortisol, 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol

What three initial screening tests evaluate suspected Cushing's disease?

Cortisol suppresses to < 1.8 mcg/dL (or < 5 mcg/dL depending on assay)

What is the normal expected cortisol response to a 1-mg overnight dexamethasone suppression test?

CRH Stimulation Test

Which dynamic biochemical test is primarily used to differentiate pituitary Cushing's disease from ectopic ACTH secretion?

Baseline FSH, LH, free alpha subunit, estrogen/testosterone, and TRH stimulation test

What diagnostic panel evaluates a suspected gonadotropin-secreting adenoma?

Inappropriately normal or elevated TSH in the setting of elevated free T4 and free T3

What unique biochemical pattern identifies a TSH-secreting pituitary adenoma?

Pituitary MRI with dedicated protocol

What imaging modality is the gold standard for searching for secondary hypothalamic-pituitary pathologies?

Medical/hormonal therapy, transsphenoidal surgery, and radiation therapy

What are the three main therapeutic modalities for hypothalamic-pituitary gland disorders?

Prolactin

Which anterior pituitary hormone is primarily responsible for lactation and parturition, but is not indispensable for human survival?

Dopamine

Which endogenous hypothalamic factor exerts continuous tonic inhibitory control over lactotroph prolactin secretion?

Serum prolactin concentration > 200 mcg/L

What threshold serum prolactin level is considered diagnostic of a prolactinoma?

Chronic renal failure, hypothyroidism, hypothalamic tumors/lesions, and medications

What conditions cause mild to moderate hyperprolactinemia (30 to 100 mcg/L) without a prolactinoma?

Antipsychotics (e.g., risperidone), antidepressants, neuroleptics, and methyldopa

Which medication classes commonly cause drug-induced hyperprolactinemia?

Amenorrhea, galactorrhea, and infertility

What classic symptom triad characterizes hyperprolactinemia in premenopausal females?

Impotence, decreased libido, erectile dysfunction, low sperm count, galactorrhea, and infertility

What clinical features characterize hyperprolactinemia in males?

Osteoporosis / decreased bone mineral density

What long-term bone complication occurs in both males and females with chronic hyperprolactinemia due to sex hormone suppression?

Pregnancy and breastfeeding / lactation

What natural physiological states must always be ruled out when evaluating hyperprolactinemia?

Fasting morning serum prolactin level < 20 mcg/L

What is the normal baseline reference level for serum prolactin in healthy adults?

Hook effect (false low reading due to assay saturation requiring sample dilution)

What laboratory artifact can cause a deceptively low prolactin reading in a patient with a massive macroprolactinoma?

Primary hypothyroidism

Which thyroid disorder must be ruled out by checking TSH and Free T4 in a patient with hyperprolactinemia?

Pituitary MRI

What is the imaging modality of choice for confirming a prolactinoma?

Prolactinoma

Which type of functional pituitary adenoma is unique because medical therapy is recommended as the first-line treatment instead of surgery?

Dopamine agonists

What class of medications represents the primary medical treatment for hyperprolactinemia and prolactinomas?

Bromocriptine and Cabergoline

What are the two most commonly prescribed dopamine agonist medications?

Cardiac valvular regurgitation / valve defects

What major cardiovascular adverse effect requires baseline 2D echocardiography monitoring in patients taking high-dose Cabergoline (>3 mg/day)?

Constipation, nasal stiffness, dry mouth, nightmares, insomnia, vertigo, nausea, and vomiting

What are common side effects associated with dopamine agonist therapy?

Bromocriptine

Which dopamine agonist is a short-acting ergot alkaloid preferred when pregnancy is desired?

Cabergoline

Which long-acting ergoline derivative is preferred overall for prolactinoma treatment due to higher efficacy and better tolerability?

0.5 to 1.0 mg twice weekly

What is the standard dosing frequency for Cabergoline in hyperprolactinemia?

Dopamine agonist resistance, medication intolerance, treatment failure, or macroprolactinoma with planned pregnancy

What are the specific indications for transsphenoidal surgery in prolactinoma?

Aggressive tumors unresponsive to dopamine agonists and poor surgical candidates

When is radiotherapy indicated for prolactinoma management?

Somatotrope pituitary adenoma

What is the underlying etiology in over 95-98% of patients presenting with acromegaly?

Chest or abdominal carcinoid tumors

What is the most common cause of ectopic GHRH-mediated acromegaly?

Insidious onset with symptoms present for at least 10 years before clinical diagnosis

What is the typical clinical timeline for the development of acromegaly symptoms?

Acral bony overgrowth, frontal bossing, enlarged hands/feet, prognathism, widened lower incisor spacing, and coarse facial features

What characteristic physical skeletal changes occur in adult acromegaly?

Pituitary Gigantism

What clinical entity develops when growth hormone hypersecretion begins during childhood before epiphyseal long bone closure?

Hyperhidrosis, deep hollow voice, oily skin, arthropathy, kyphosis, carpal tunnel syndrome, and generalized visceromegaly

What soft tissue and systemic manifestations accompany skeletal overgrowth in acromegaly?

Cardiovascular system

Which organ system complication is the primary cause of morbidity and premature mortality in acromegaly?

Arrhythmias, cardiomyopathy, left ventricular hypertrophy, and decreased diastolic function

What specific cardiac complications occur in patients with acromegaly?

Type 2 Diabetes Mellitus

What metabolic disorder develops in up to 25% of acromegaly patients because GH counteracts insulin action?

Colonic polyps and dolichomegacolon

What gastrointestinal lesions require screening colonoscopy in patients with acromegaly?

Three-fold (3x) increased mortality

By how much is overall mortality increased in untreated acromegaly?

Age-matched serum IGF-1 concentration

What is the initial screening blood test of choice for acromegaly?

Failure of serum GH to suppress to < 0.4 mcg/L (or < 1 mcg/L) within 1-2 hours of a 75g oral glucose load

What constitutes a positive confirmatory Oral Glucose Tolerance Test (OGTT) for acromegaly?

Pituitary MRI

What imaging study is performed immediately following a positive biochemical confirmation of acromegaly?

Chest and abdominal CT scan to look for carcinoid tumors, and serum GHRH measurement

What diagnostic evaluations should be performed if a patient has confirmed acromegaly but a normal pituitary MRI?

Normalization of serum IGF-1 levels

What is the primary biochemical goal and marker of disease control throughout the management of acromegaly?

Transsphenoidal surgical resection

What is the recommended first-line treatment for all functional GH-secreting pituitary adenomas?

Within 3 to 4 days post-operatively

How quickly do serum IGF-1 levels normalize following successful complete transsphenoidal resection of a GH adenoma?

Octreotide acetate, Lanreotide, and Pasireotide

Which Somatostatin Receptor Ligands (SRLs) are used as adjuvant medical therapy for acromegaly?

Hyperglycemia (due to potent inhibition of pancreatic insulin secretion via SST5 receptors)

What prominent metabolic side effect is uniquely associated with Pasireotide LAR?

Pegvisomant

Which drug functions as a GH receptor antagonist by blocking peripheral GH binding to its receptor?

Serum GH levels remain elevated while IGF-1 levels fall

What happens to serum GH versus IGF-1 levels during Pegvisomant therapy?

Serial pituitary MRI scans

How must tumor size be monitored in an acromegaly patient managed with Pegvisomant?

Hypothalamic-pituitary damage leading to progressive hypopituitarism

What major long-term adverse effect can result from stereotactic radiation therapy for acromegaly?

ACTH-producing pituitary corticotrope adenoma (Cushing's Disease)

What is the most common cause of endogenous Cushing's syndrome?

Iatrogenic / exogenous glucocorticoid (steroid) administration

What is the most common cause overall of Cushingoid physical features?

Responds to high-dose glucocorticoid suppression

How does a pituitary ACTH-secreting adenoma respond to high-dose glucocorticoid feedback compared to ectopic tumors?

Progressive central obesity and weight gain

What is the most frequent clinical sign observed in patients with Cushing's syndrome?

Thin skin, moon facies, facial plethora, purple striae, hirsutism, hypertension, and proximal muscle weakness

What physical features result from chronic tissue exposure to excess cortisol?

24-hour urine free cortisol (UFC), 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol

What three screening tests demonstrate pathological hypercortisolism?

At least 2 positive test results

How many abnormal test results are required for 24-hour UFC or late-night salivary cortisol to confirm hypercortisolism?

1 positive test result

How many abnormal test results are required for the 1-mg overnight dexamethasone suppression test to suggest hypercortisolism?

Inferior Petrosal Sinus Sampling (IPSS) / Inferior Petrosal Venous Sampling

What is the gold standard diagnostic procedure to differentiate a pituitary ACTH source from an ectopic ACTH source?

Central to peripheral ACTH ratio > 2 at baseline, or > 3 after CRH stimulation

What central-to-peripheral ACTH gradient on IPSS confirms Cushing's Disease?

Central to peripheral ACTH ratio < 2 at baseline, or < 3 after CRH stimulation

What central-to-peripheral ACTH gradient on IPSS indicates an ectopic ACTH-secreting tumor?

Pituitary corticotrope adenomas are more common in females with slow onset, whereas ectopic ACTH tumors are more common in males with rapid onset

How do Cushing's disease and ectopic ACTH syndrome differ regarding sex distribution and clinical onset?

Severe hypokalemia (<3.3 mmol/L or 75% of cases) and hyperpigmentation

What electrolyte and dermatologic features are prominently associated with ectopic ACTH secretion compared to Cushing's disease?

Small cell lung cancer and bronchial carcinoid tumors

What are the most common extrapituitary malignancies causing ectopic ACTH syndrome?

Transsphenoidal surgical resection of the pituitary adenoma

What is the first-line treatment of choice for Cushing's disease?

Transient central adrenal insufficiency requiring temporary hydrocortisone replacement

What endocrine deficiency is expected immediately following successful surgical cure of Cushing's disease?

Mifepristone

Which glucocorticoid receptor antagonist blocks the peripheral actions of cortisol and improves hyperglycemia in Cushing's syndrome?

Metyrapone

Which oral adrenal steroidogenesis inhibitor works by blocking 11-beta hydroxylase activity?

Mitotane

Which adrenolytic agent destroys adrenocortical cells and is used for adrenal carcinoma and persistent Cushing's?