Endocrinopathies are classified as primary, secondary, or tertiary.

  • Primary endocrine disease inhibits the action of downstream glands/ target endocrine glands.
  • Secondary endocrine disease is indicative of a problem with the pituitary gland.
  • Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.

Vasopression excess (SIADH)

Causes:

1) Ectopic production by carcinoma of lungs & pancreas
2) CNS: Trauma, infections ,tumours
3) Drug induced: Chlopropamide, Nicotine, Morphine

Pathophysiology:

  • Antidiuresis
  • Water reabsorption
  • Concentrated urine (inappropriately high urine osmolality)
  • Diluted plasma (low plasma osmolality)
  • Dilutional water expansion (ECF > 10%) inhibit aldosterone secretion
  • Increase renal excretion of NA+ (SALT WASTING) –> Hyponatraemia.

Therefore, from the evaluation of concentrated urine, low plasma osmolality and hyponatraemia can diagnose SIADH.

Management:

  • Restrict water intake (prevent plasma dilution)
  • Block renal action. Give (Demeclocycline: V2 receptor antagonist. interferes with cAMP production, reverse antidiuresis effect)
  • Replace Na+ loss in urine (oral salt, same as diarrhea)
  • Treat cause of SIADH

Vasopressin Deficiency (Diabetes Insipidus)

Pathophysiology:

  • Water diuresis (Polyuria)
  • Increase plasma osmolality, decrease plasma volume
  • thirst centre (hypothalamus)
  • thirst, polydipsia

2 types:

1) Cranial DI (Central/Neurogenic)

Defective/ decreased production of vasopressin by the hypothalamo-neurohypophyseal system (Hypothalamus/ Post pituitary)

2) Nephrogenic DI

Defective renal response to vasopressin (hormone resistance)
Defective V2 vasopressin receptors in kidney (receptor disease)
Defective water channel proteins (aquaporins)

Dynamic (Stimulation) Tests for Vasopressin:

By intentionally raising the plasma osmolality (less water) and monitor whether the vasopressin secretion increases (osmoregulation). Raising the plasma osmolality can be done by water deprivation/ infusion of hypertonic saline.

Water deprivation test:

  • Record serum & urine osmolality & body weight every 2 hours (up to 8 hours)
  • No fluids given during the test
  • DI diagnosed if: serum osmolality rises to above normal. Urine osmolality remains low (failure of antidiuresis, watery urine)

Differentiate Cranial & Nephrogenic DI:

  • Give a synthetic Vasopressin analogue: DDAVP (des-amino-des-aspartate AVP/ Desmopressin) intramuscularly. It has more renal effect than vasoconstrictor effect, so relatively pleasant for the patient.
  • Due to the antidiuretic effect, the urine becomes concentrated. Therefore, it is proven that the defect is at the cranial level, meaning that there is decreased production of vasopressin by the posterior pituitary. The distal nephron is responsive to DDAVP. —– Cranial DI
  • If the urine still fails to concentrate, and remain diluted, it means the distal nephron is not responsive to DDAVP. Therefore it is defect at the nephron level. —– Nephrogenic DI

Observe the 2nd graph, the black arrow indicates when the DDAVP is administered. Upon administration, patient with CDI (Cranial) urine osmolality increases. Whereas, NDI (nephrogenic) the osmolality remains low.

Growth Hormone Deficiency

Read growth hormone lecture before continuing.

Pituitary dwarf

Due to lack of GH. Due to this, pituitary dwarfs will present as:

  • have systemic illnesses (organ growth retardation)
  • deprivation/psychosocial dwarfism: mental retardation
  • late/no pubertal development
  • unproportional body
  • lack of growth, young bone age

Laron dwarf

Due to lack of IGF-1. hGH receptor defect in liver – inability to produce IFG-1 – decrease growth eventhough GH level normal.

Evaluation of GH deficiency:

Measure serum GH after stimulating the GH secretion (Dynamic Provocative Stimulation Tests) by:

  • Providing GHRH
  • Insulin tolerance test (inject insulin)
  • Post-exercise bloog sample
  • 1 hour after going to sleep

If serum levels increase: enough reserve
If serum levels remain the same: deficiency in GH

Identify source of problem: primary, secondary / tertiery.
Eg: If GHRH provided and GH level increase, meaning problem is at the hypothalamus. If GHRH provided and GH level remain low, meaning problem is at the pituitary. If GH increase, but IGF-1 low, meaning problem is at the target organ.

Growth hormone excess

Gigantism & Acromegaly
Only difference is acromegaly still will be able to cause excessive long bone growth due to open epiphyseal plate.

Other problems of growth hormone excess:

  • Bitemporal hemianopia (Tumour compress optic chiasma)
  • Frontal bossing, protruding mandible (prognatism)
  • Hirsutism
  • Gynecomastia & lactation
  • Osteoarthritic vertebral changes
  • Visceromegaly (heart, liver, kidneys)
  • Thickened, sweaty & greasy (increased sebum secretion, handshake)
  • Enlarged hands & feet (tight ring, increasing shoe size)
  • Diabetes mellitus (anti-insulin effect, FA as prefered fuel instead)

Lab evaluation on growth hormone excess:

  • Raised GH & IGF-1 (important! Synergistic)
  • Absense of nocturnal rise of serum GH (rise whole day, circadian rhythm distrupted)
  • Oral glucose tolerance test
    Normal: Hyperglycemia suppress glucose
  • Neuro-radiological accessment: Tumour of anterior pituitary.

Hyperprolactinaemia

High levels of prolactin causes suppression of sex hormones (gonadotropes) – hypogonadism – amenorrhea & infertility. Prolactin also causes milk synthesis and secretion therefore galactorrhoea (spontaneous flow of milk) will be present.

Evaluation:

After excluding stress, pregnancy and drugs which will also cause increase in plasma prolactin levels, confirmation of hyperprolactinemia. Next will be to do a neuro-radiological assessment of the pituitary gland, to look for tumour. As discussed in pituitary tumours , the mass effect of the tumour will compress the pituitary stalk, which will cause increase prolactin production and release, this phenomenon is ‘stalk effect’.

Thyroid hormone deficiency & excess

Read more in hypothyroidism & hyperthyroidism.

As a basic recap,

Hypothalamus — Thyrotropin releasing hormone (TRH) — Anterior Pituitary — Thyrotropin/ Thyroid stimulating hormone (TSH) — Thyroid — T3,T4.

Evaluation for hypothyroid:

  • TRH, TSH normal. T3, T4 low
    : Primary
  • TRH normal. TSH low. T3, T4 low: Secondary
  • TRH low. TSH low. T4, T4 low: Tertiery

IF given TRH injection, TSH normal: Hypothalamic defect. If TSH remain low: Pituitary defect.

Hypothyroidism:

In the case of maternal iodine deficiency –> may cause neonatal hypothyroidism/ cretin.

image

A cretin child:

  • large tongue
  • coarse features
  • nostrils lower than base of the nose
  • darker skin
  • mental retardation
  • short stature
  • reproductively ineffective (no breast) ?
  • Child-like

Treatment for cretin:

Give serum TSH –> if serum T4 decreased/remain low: T4 replacement therapy as treatment.

Hyperthyroidism:

Hyperthyroidism can cause thyrotoxicosis (Grave’s disease)

Cause of hyperthyroidism:

  • TSH receptor-stimulating antibodies ( on thyroid gland, cause release of excessive T4, T3)
  • Functional anterior pituitary/hypothalamic tumours

Evaluation:

T3 suppression test:

Large doses of T3 given – negative feedback to hypothalamus & anterior pituitary – normal: TSH suppressed.

If TSH not suppressed: Tumour (autonomous)

Panhypopituitarism

Panhypopituitarism is the deficiency in pituitary hormone production. The sequence of loss of hormonal secretion is as follow:

  1. hGH
  2. LH
  3. FSH
  4. ACTH
  5. TSH

Causes:

Find out the Nine I’s from Greenspan.
+ Genetic causes

Investigations:

Stimulation tests for:

  • hCG ( GHRH test, Insulin tolerance test) — GH
  • LH, FSH (GnRH test)
  • ACTH (CRH test, Insulin tolerance test)
  • TSH ( free T3,T4, TSH)

Sequential injection of GHRH, GnRH, CRH — Then measure serum GH, LH, FSH & ACTH.

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