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Disorders of Endocrine Function – Vocabulary Flashcards

Basic Concepts of Endocrine Disorders

  • Etiologic categories ("why" the gland or pathway fails or over-functions)- Congenital: genetic/embryologic malformation → life-long hormone deficit or excess.

    • Infectious: e.g., viral thyroiditis damaging follicular cells.

    • Autoimmune: self-reactive antibodies destroy or stimulate glands (Hashimoto, Graves, Type 1 DM parallels).

    • Neoplastic: benign or malignant tumors that obliterate tissue (↓) or hyper-secrete (↑).

    • Idiopathic: no identifiable cause; may hide undiscovered mechanisms.

    • Iatrogenic: physician-induced (e.g., surgery, radiation, glucocorticoid drugs).

  • Levels of pathogenesis- Primary disorder: intrinsic to the target gland itself (e.g., thyroidectomy → primary hypothyroidism).

    • Secondary disorder: pituitary origin—trophic hormone (ACTH, TSH, etc.) abnormal.

    • (Implied) Tertiary disorder: hypothalamic dysfunction (CRH, TRH, GnRH).

    • Clinical pearl: Feedback loops invert lab patterns—e.g., primary gland failure → target hormone ↓, trophic hormone ↑.

Growth Hormone (GH) Disorders

  • Physiology recap

    • GH → liver → insulin-like growth factor-1 (IGF-1 a.k.a. somatomedin) → linear bone growth, protein synthesis.

    • Secreted in pulsatile bursts, ↑ during sleep/exercise; inhibited by somatostatin.

  • GH Deficiency

    • Mechanistic categories

    • Decreased GH secretion (hypopituitarism, hypothalamic lesions, idiopathic).

    • Defective GH molecule or receptor → "bio-inactive" hormone.

    • Impaired IGF-1 generation (liver disease, GH-insensitive Laron dwarfism).

    • Clinical impact

    • Children: ↓ linear growth → proportionate short stature; delayed bone age; normal intelligence.

    • Adults (acquired): ↓ lean mass, ↑ fat, hyperlipidemia, diminished well-being.

    • Diagnostics: low random or provoked GH, low IGF-1, MRI for pituitary lesion.

  • GH Excess

    • Usual cause: pituitary adenoma (>95 %).

    • Timing dictates phenotype

    • Before epiphyseal closure (childhood/adolescence): gigantism → rapid, symmetrical skeletal overgrowth, may reach >2.4 m tall.

    • After epiphyses fused (adulthood): acromegaly → acral & soft-tissue enlargement (hands, feet, jaw), organomegaly, insulin resistance.

    • Complications: cardiomyopathy, sleep apnea, colon polyps, arthropathy.

Thyroid Hormone Disorders

  • Hormone basics- Thyroxine T4 (pro-hormone), Tri-iodothyronine T3 (active). Require iodine + thyroglobulin substrate; controlled by TSH.

Hypothyroidism

  • Forms- Congenital: agenesis, dysgenesis, or dyshormonogenesis → cretinism if untreated.

    • Acquired – usually primary (≈95 %): Hashimoto thyroiditis (autoimmune destruction), iatrogenic (131-I ablation, surgery), severe iodine deficiency.

  • Iodine deficiency pathophysiology- Cannot iodinate tyrosyl residues ⇒ thyroglobulin accumulates ⇒ colloid goiter even though T3/T4 low.

  • Clinical features- Goiter: enlarged gland may occur in hypo-, eu-, or hyperthyroid states (compensatory TSH drive, cysts, tumors).

    • Myxedema: non-pitting mucopolysaccharide edema (face, larynx, hands) due to long-standing severe deficiency; risk of myxedema coma (↓ mental status, hypothermia).

Hyperthyroidism (Thyrotoxicosis)

  • Mechanisms1. Follicular hyperfunction with ↑ hormone synthesis/secretion

    • Graves disease: IgG autoantibodies (TSI) bind TSH receptor → diffuse goiter, ophthalmopathy.

    1. Follicular cell destruction releasing pre-formed hormone

    • Subacute (de Quervain) or Hashimoto thyroiditis early phase.

    1. Exogenous: ingestion of excess hormone (factitious thyrotoxicosis, weight-loss abuse).

  • Hallmark labs: ↑ T3/T4, ↓ TSH (except in TSH-secreting tumors).

  • Clinical hyper-metabolic effects: weight loss, heat intolerance, tremor, palpitations, hyperdefecation, osteoporosis.

Adrenocortical Hormone Disorders

Overview of Cortex

  • Zona glomerulosa → mineralocorticoids (aldosterone)

  • Zona fasciculata → glucocorticoids (cortisol)

  • Zona reticularis → androgens.

Adrenocortical Insufficiency

  • Primary (Addison disease)- Autoimmune adrenalitis (70 %), infections (TB, HIV), metastasis.

    • Both cortisol & aldosterone low → hypotension, hyperkalemia, hyperpigmentation (↑ACTH → \alpha-MSH).

  • Secondary- Pituitary ACTH deficiency (exogenous steroid withdrawal, tumors).

    • Aldosterone usually preserved (RAAS intact).

  • Tertiary- Hypothalamic ↓CRH (trauma, tumors), or abrupt cessation of long-term steroids > suppresses CRH/ACTH axis.

Congenital Adrenal Hyperplasia (CAH)

  • Enzyme block (most commonly 21\alpha-hydroxylase deficiency)- ↓ cortisol → ↑ ACTH → adrenal hyperplasia.

    • Precursors shunted to androgens → virilization.

    • Female neonate: ambiguous genitalia (enlarged clitoris, fused labia).

    • Male neonate: macropenis, early pigmentation; salt-wasting crises if mineralocorticoid block.

Hypercortisolism

  • Etiology tiers- Primary: adrenal adenoma/carcinoma (ACTH independent).

    • Secondary: pituitary corticotroph adenoma = Cushing disease (ACTH dependent).

    • Tertiary: hypothalamic CRH overdrive.

    • Exogenous: chronic pharmacologic glucocorticoids (most common overall).

  • "Cushing syndrome" = clinical phenotype regardless of cause; "Cushing disease" = pituitary ACTH source.

  • Manifestations: centripetal obesity, moon facies, buffalo hump, purple striae, glucose intolerance, muscle wasting, osteopenia, mood changes, ↑ infection risk.

Hyperaldosteronism

  • Primary (Conn syndrome): aldosterone-producing adenoma or bilateral hyperplasia; ↓ renin.

  • Secondary: renal hypoperfusion (heart failure, cirrhosis, nephrotic syndrome) → RAAS activation; ↑ renin.

  • Effects: Na^+ & water retention → hypertension; renal K^+ & H^+ wasting → hypokalemic alkalosis.

Adrenal Medulla Disorder

  • Physiology: chromaffin cells secrete epinephrine > norepinephrine under sympathetic stimulation; rapid catecholamine burst = "fight or flight".

  • Pheochromocytoma- Catecholamine-secreting tumor, 90 % in adrenal medulla (rule of 10 % extra-adrenal, malignant, familial).

    • Paroxysmal or sustained hypertension, pounding headache, tachycardia, diaphoresis, tremor, anxiety, weight loss.

    • "Rule of P's": Pressure (↑BP), Pain (headache), Perspiration, Palpitations, Pallor.

Parathyroid Gland Disorders

  • PTH physiology: ↑ serum Ca^{2+} (bone resorption, kidney reabsorption, vitamin D activation) & ↓ PO_4^{3-} reabsorption.

Hyperparathyroidism

  • Primary: adenoma (85 %), hyperplasia, carcinoma; autonomous secretion.

  • Secondary: chronic hypocalcemia (CKD) → compensatory PTH ↑.

  • Consequences: hypercalcemia → stones, bones, groans, psychiatric overtones; cortical bone demineralization (osteitis fibrosa cystica).

Hypoparathyroidism

  • Causes: postsurgical removal, autoimmune, congenital DiGeorge syndrome.

  • Low Ca^{2+} → neuromuscular excitability: tetany, Chvostek & Trousseau signs, seizures, laryngospasm.

Antidiuretic Hormone (ADH) Disorders

  • ADH (vasopressin) acts on V2 receptors → H_2O reabsorption in collecting ducts → concentrate urine.

Diabetes Insipidus (DI)

  • Pathophysiology: inadequate ADH (central) or renal insensitivity (nephrogenic).

  • Cardinal signs: polyuria (>3 L/day), polydipsia, dilute urine (U-osm <300 mOsm/kg), hypernatremia.

  • Complications: dehydration → lethargy, disorientation, seizures; absence of diaphoresis despite hyperthermia risk.

  • Water-deprivation test: failure to concentrate urine distinguishes DI.

Syndrome of Inappropriate ADH Secretion (SIADH)

  • Excessive ADH (often ectopic from small-cell lung cancer, CNS disorders, drugs).

  • Consequence: water retention → dilutional hyponatremia (Na < 135\,\text{mEq/L}) with euvolemia; urine inappropriately concentrated.

  • Symptoms: nausea, headache, confusion, seizures due to cerebral edema.

Integration & Clinical Connections

  • Feedback loops: Primary gland hypo-state → low end hormone, high trophic; hyper-state inverse. Testing patterns guide localization.

  • Neonatal screening for congenital hypothyroidism & CAH prevents irreversible cognitive impairment & salt-wasting crises: ethical imperative.

  • Exogenous glucocorticoid therapy: benefits vs. risk of iatrogenic Cushing & adrenal suppression; necessitates tapering – practical pharmacology.

  • Endocrine tumors (adenomas, pheochromocytomas) often benign but hormonal excess creates morbidity; underscores role of biochemical testing before imaging.

  • Multisystem impact: Endocrine disorders seldom isolated; monitor cardiovascular, metabolic, skeletal, neuropsychiatric sequelae.

  • Social aspects: Short stature or acromegaly affects psychosocial health; clinicians must address quality-of-life, not solely lab norms.