Endocrinology/Clinical disorders

From PhysioWiki

Contents 1 Hypogonadotropic hypogonadism (Kallman syndrome) 2 Primary adrenal insufficiency (Addison's disease) 3 Secondary adrenal insufficiency 4 Cushing's syndrome 5 Primary aldosteronism (Conn's syndrome) 6 Secondary aldosteronism 7 Congenital adrenal hyperplasia (adrenogenital syndrome) 7.1 Due to 21α-hydroxylase deficiency 7.2 Due to 11β-hydroxylase deficiency 7.3 Other causes 8 Primary hypogonadism 9 Secondary hypogonadism 10 5α-reductase deficiency 11 Androgen insensitivity (testicular feminization) 12 Benign prostatic hypertrophy 13 Polycystic ovarian syndrome (Stein-Leventhal syndrome) 14 Chronic stress 15 Leydig cell and arrhenoblastoma tumors 16 Granulosa-theca cell tumors 17 Intraovarian adrenal rests 18 Hydatidiform mole, choriocarcinoma 19 Osteoporosis 20 Osteomalacia 21 Paget disease of bone 22 Renal disease 23 Hypothyroidism 24 Multiple endocrine neoplasia (MEN) 24.1 Type 1 24.2 Type 2 25 Hirschsprung disease

Hypogonadotropic hypogonadism (Kallman syndrome)

• ↓GnRH is underlying disorder; could result from failure of GnRH neurons to migrate to hypothalamus from olfactory epithelium
• ↓GnRH → ↓LH, ↓FSH → ↓testosterone → hypogonadism, feminine body type, ↓sense of well-being, depression
• Treat with testosterone

Primary adrenal insufficiency (Addison's disease)

• Antibodies against adrenal cortex → ↓cortisol, ↓aldosterone
• ↓Cortisol
  • Hypoglycemia
  • Intolerance to stress
  • Insulin hypersensitivity
  • Weight loss possible
  • ↓Negative long-loop feedback on ACTH release → ↑POMC
    • ↑POMC → ↑ACTH, ↑MSH, ↑endorphins
    • ↑MSH → ↑pigmentation
    • ↑ACTH → adrenal hyperplasia
• ↓Aldosterone → ↓Na⁺, ↑K⁺
  • ↓Na⁺ → ↓BP (hypotension)
  • ↑K⁺ → ↓pH
• Treat with cortisol

Secondary adrenal insufficiency

• ↓ACTH due to anterior pituitary necrosis (e.g. from hemorrhage), for example
• Pathophysiology same as 1° insufficiency, but without hyperpigmentation

Cushing's syndrome

• ↑Cortisol from adrenal adenoma, Cushing's disease (ACTH-secreting pituitary adenoma), or iatrogenic (e.g. prednisone)
• Truncal obesity, moon face, buffalo hump
• ↑Cortisol → ↑gluconeogenesis, ↓immune function (decreased resistance to infection, diminished inflammatory response)
• ↑Cortisol acts as mineralocorticoid → ↑BP, edema, ↓K⁺, ↑pH (alkalosis)

Primary aldosteronism (Conn's syndrome)

• Primary disorder: ↑aldosterone due to tumor of zona glomerulosa
• ↑Aldosterone → ↑Na⁺, ↓K⁺
• ↑Na⁺ (hypernatremia) → ↑water retention → ↑BP
• ↓K⁺ (hypokalemia) → weakness, ↑pH (alkalosis)
• ↑Na⁺, ↓K⁺, ↑aldosterone → ↓renin → ↓angiotensin

Secondary aldosteronism

• Renal artery stenosis → JG cells detect ↓BP → ↑renin → ↑AII → ↑aldosterone
• Pathophysiology same as 1° aldosteronism

Congenital adrenal hyperplasia (adrenogenital syndrome)

Wikipedia has some nice write-ups on CAH written by an endocrinologist in case you're interested. Here's the gist:

Due to 21α-hydroxylase deficiency

• Accounts for 90-95% of CAH cases
• Primary disorder: ↓21-hydroxylase → ↓cortisol, ↓aldosterone
• ↓Cortisol → ↑ACTH → adrenal hyperplasia
• ↓Aldosterone → ↓Na⁺, ↑K⁺, ↓BP, ↓pH (acidemia)
• ↑Precursor backup → ↑androgens (by mass action)
• ↑Androgens → ↑body growth, ↑virilization, ambiguous external genitalia in XX individuals
• Treat with glucocorticoid and mineralocorticoid replacement (e.g. prednisone and fludrocortisone)

Due to 11β-hydroxylase deficiency

• Accounts for most of the remaining cases
• Primary disorder: ↓11β-hydroxylase → ↓cortisol
• ↑Precursor backup → same symptoms as above minus the salt-wasting, since a mineralocorticoid (11-DOC) is produced as a by-product. 11-DOC is 10 times as strong as aldosterone in its salt-retaining effects
• Treat with glucocorticoid replacement (e.g. prednisone)

Other causes

• Could be caused by 17-hydroxylase deficiency, but we weren't responsible for knowing this.

Primary hypogonadism

• ↓Testosterone due to enzyme deficiency in testis
• Lack or regression of secondary sex characteristics

Secondary hypogonadism

• ↓LH and/or ↓FSH (possibly ↓GnRH as well?)

5α-reductase deficiency

• ↓5α-reductase → ↓DHT
• XY individual has external female genitalia (internal male)
• Inguinal testes
• ↑Testosterone at puberty → masculinization
• Hypospadias (urethral meatus not in penis)

Androgen insensitivity (testicular feminization)

• No functional androgen receptors
• Internal male genitalia in XY individuals (due to presence of Y chromosome and anti-mullerian hormone)
• ↑Testosterone synthesis → ↑conversion to estrogens (by mass action)
• ↑Estrogens → external female genitalia in XY individuals

Benign prostatic hypertrophy

• Occurs in 75% of men over 60
• Mechanism poorly understood; appears to involve sex steroids

Polycystic ovarian syndrome (Stein-Leventhal syndrome)

• ↑Insulin is underlying disorder
• ↑Insulin → ↑androgens from thecal cells (in normal individual, would diffuse to granulosa cells and be converted to estradiol)
• ↑Androgens → ↑estrone by mass action (excess androgens converted to estrone in adipocytes)
• ↑Estrone → change pattern of GnRH secretion → ↑LH, ↓FSH
  • ↑LH → ↑androgens from thecal cells
  • ↓FSH → ↓aromatase in granulosa cells → ↓conversion of androgens to estradiol
  • ↑Androgens → ↑conversion by aromatase to estrone in adipocytes (by mass action, as above)
  • Net result is ↑androgens, ↑estrone (positive feedback)
• ↑Androgens → virilization
• Exacerbated by obesity:
  • Type II diabetes → insulin resistance → ↑insulin
  • ↑Fat → ↑conversion of androgens to estrone → ↑LH, ↓FSH
• Exacerbated by chronic stress: ↑CRH → ↑cortisol → ↑glucose → ↑insulin
• Treat with an estrone antagonist such as clomiphene

Chronic stress

• ↑CRH → ↑opiods → ↓GnRH → amenorrhea, infertility

Leydig cell and arrhenoblastoma tumors

• Produce testosterone

Granulosa-theca cell tumors

• Produce estrogens

Intraovarian adrenal rests

• Produce cortisol

Hydatidiform mole, choriocarcinoma

• Produce hCG

Osteoporosis

• Normal bone in isufficient quantities
• Mechanism
  • ↓Ovarian estrogen synthesis at menopause
  • Estrone made from androstenedione in adrenals
  • Estrone is insufficient for bone upkeep
• May result from post-immobilization osteopenia (which may recover in 2-3 weeks)

Osteomalacia

• ↓Hydroxyapetite → abnormal bone
• Greater osteoid surface (much more than normal 16% value)
• Weak bones, very elastic
• Closely related to rickets, which is osteomalacia in growing bones

Paget disease of bone

• Trabeculae do not orient along lines of force → abnormal bone
• Weak bones → ↑fractures, ↑↑bone density (to compensate)

Renal disease

• Improper Ca²⁺:PO₄^2- ratio → abnormal bone
• Uremia → ↓osteoclasts

Hypothyroidism

• Primary (due to abnormal thyroid gland) or secondary (due to ↓TRH, ↓TSH, iodide deficiency, etc.)
• Result is ↓T₃ and ↓T₄
• ↓Basal metabolic rate → ↑weight gain
• ↓Thermogenesis → cold intolerance
• ↓Mental function → somnolence
• ↑Cholesterol
• Myxedema (non-pitting edema)

Multiple endocrine neoplasia (MEN)

Type 1

From Sherman's lectures.

Type 2

• Etiology: Gain-of-function mutation in RET RTK gene
• Syndrome:
  • Medullary thyroid carcinoma
  • Pheochromocytoma
  • Hyperparathyroidism

Hirschsprung disease

• Etiology: Loss-of-function mutation in RET RTK gene
• Consequences:
  • Aganglionosis of the gut
  • Lack of innervation to the hindgut