Endocrinology

Sodium and water balance

Hyponatraemia

Introduction

  • A low serum Na means a low serum osmolality which causes cellular oedema from osmotic shifts of water into cells. Rapid sudden changes can cause irreversible neuronal damage.

Clinical

  • Mild < 130 mmol/l :
  • Symptoms of lethargy
  • Moderate < 120 mmol/l : Headchae, nausea, cramps, confusion
  • Severe < 110 mmol/l : Confusion, Seizure, delirium Coma, death

Investigations

  • U&E - low Na
  • Urinary Na < 20 mmol where there is hypovolaemia and Na retention
  • Urinary Na > 20 mmol where there is no hypovolaemia or there is salt wasting from renal or cerebral disease
  • Check Cortisol levels - Short synACTHen if Adrenal failure considered (low BP and hypovolaemic, pigmentation)
  • Check TFTs

Management

  • Expert help in difficult cases
  • Water overload : Restritct fluids
  • Salt loss exceeds water loss : IV N-Saline
  • IM Hydrocortisone if adrenal failure considered

Syndrome of Inappropriate ADH (SIADH)

Introduction

  • ADH (vasopressin) is a hormone produced in the supraoptic and paraventricular nuclei in the hypothalamus released by the posterior pituitary usually primarily in response to a change in serum osmolality
  • It prevents the loss of water in the collecting ducts
  • There it is released with any rise in plasma osmolality
  • The action is via G receptors in the corticomedullary collecting ducts by which aquaporins are inserted into the cells lining the lumen making them more permeable to water
  • However in some situations ADH is released in high levels inappropriately
  • Before one can make the diagnosis one must be sure that adrenal and thyroid function is normal
  • Patients become water intoxicated.

Causes

  • Pituitary surgery and Cerebral disease - meningitis, encephalitis, GBS, SAH, Stroke, Bleed
  • Acute intermittent porphyria
  • Drugs - chlorpropamide, barbiturates, anaesthetics, barbiturates, morphine, diuretics, vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan, Opiates and narcotic analgesics
  • Malignancies - primary brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and prostatic cancer, and sarcomas especially small cell lung cancer
  • Respiratory - Positive pressure ventilation, pneumonia, and lung abscess.

Clinical :

  • Patient is clinically euvolaemic
  • Findings depend on degree of hyponatraemia.
  • Ranges from asymptomatic to those with lethargy, confusion/delirium and even Fits

Investigations

  • Serum Na low
  • Urine Na > 20 mmol/l
  • Urine osmolality > Serum osmolality
  • Normal TFTs, Adrenal function, Glucose, Renal

Management

  • Slow controlled correction by fluid restriction to 800-1000 mol/day
  • Refractory cases - demeclocyline to induce nephrogenic diabetes insipidus
  • Too rapid correction can cause quadriplegia and brainstem signs - Central pontine myelinosis

Cerebral salt wasting

Introduction

  • A syndrome by which cerebral injury leads to a urinary salt loss with resultant hyponatraemia which must be differentiated form those with SIADH

Clinical

  • Signs of head injury or SAH. Polyuria
  • Dehydration - hypotension, tachycardia

Investigations

  • Serum Na low
  • Urine Na > 20 mmol/l and tends to be higher than with SIADH
  • Urine output > 2500 mls/day

Management

  • The treatment is with salt and volume replacement which is opposite to the fluid restriction needed for SIADH
  • Treatment is water and salt replacement
  • Consider fludrocortisone

Hypernatraemia

Introduction

  • Is usually due to excess free water loss
  • Polyuria - measure urine volume > 3 L/day

Causes

  • Severe dehydration e.g. lost in the desert or immobile and forgotten in the ward side-room
  • Hyperosmolar non ketotic coma (HONK) with severe glycosuria
  • Cranial Diabetes Insipidus, Nephrogenic diabetes insipidus
  • Severe hypercalcaemia, Hyperglycaemia
  • Diuretics, Hypokalaemia
  • Potomania, Renal failure with impaired concentrating ability
  • Post SVT and ANP release

Management

  • Determine underlying cause
  • Water replacement and rehydration

Diabetes Insipidus

Introduction

  • There is a failure to reabsorb water in the collecting tubules due to either an absence of ADH (Cranial) or insensitivity to ADH (Renal).

Causes

  • Nephrogenic
    • Hypokalaemia, hypercalcaemia, lithium, familial, chronic kidney disease and Demeclocycline.
  • Cranial
    • Usually posterior pituitary damageLocal destructive lesion, trauma, surgical Usually improve with time.

Clinical

  • Polyuria > 3 L (up to 20 L/day ) /day even despite severe dehydration and serum osmolality > 300 mosm/l
  • Polydipsia

Investigations

  • Hypernatraemia if water access limited
  • Ensure normal Calcium, K, Glucose
  • Water deprivation will show urine osmolality < 300 mosm/l relative to serum osmolality > 295 mosm/l
  • Beware extreme dehydration (body weight falls > 5%)
  • Those with psychogenic polydipsia will have oliguria.
  • Give desmopressin an analogue of ADH with a longer half life which will reduce polyuria in those with cranial DI
  • MRI of head to look for pituitary or hypothalamic lesion when cranial diabetes diagnosed

Management

  • Ensure adequate access to free water and if not will need IV rehydration.
  • Cranial
    • Give intranasal desmopressin an analogue of ADH with a longer half life which will reduce polyuria. It is given usually im or intranasal metered dose spray. Be careful of hyponatraemia and water intoxication

  • Nephrogenic
    • Treat cause. Ensure adequate water intake. The polyuria is helped by Bendroflumethiazide 2.5-5 mg / Amiloride 5-10 mg/day and some use Indomethacin. Diuretics to treat polyuria - a paradoxical effects - possibly due to constriction of the vascular space and some animal studies suggest that thiazides have a specific effect of increasing collecting duct water uptake. The role of the amiloride is to avoid hypokalaemia which can worsen polyuria

Male Hypogonadism

Introduction

  • Male Hypogonadism refers to reduced gonadal function which is due to either a primary testicular problem or a secondary (pituitary/hypothalamic) disorder.
  • Testicular (Primary) Causes - Klinefelter's syndrome, Cryptorchidism, Previous Orchitis, Previous chemotherapy or radiotherapy, Testicular trauma, Bilateral testicular torsion, Alcohol excess, Chronic illness
  • Non Testicular (Secondary) Causes - Hypothalamic tumours, Kallmann's syndrome, Idiopathic hypogonadotropic hypogonadism, Pituitary disease

Clinical

  • Small testes, not fully formed genitalia
  • Loss of libido, Infertility, Impotence
  • Decreased shaving, Muscle weakness
  • Delayed puberty, Gynaecomastia
  • High-pitched voice, a small scrotum, Decreased phallic and testicular growth
  • Sparse pubic and axillary hair, and an absence of body hair
  • Absent secondary sexual characteristics
  • Osteoporosis, Absent beard growth and male pattern baldness in male
  • Poor muscle bulk, Female fat distribution in male
  • Anosmia (Kallmann's)

Investigations

  • Low testosterone seen in primary and secondary
  • Low FSH/LH seen in secondary pituitary dysfunction
  • Prolactin may be high with prolactinoma
  • Sperm count reduced
  • Sex Hormone Binding globulin enables calculation of free testosterone index
  • Pituitary MRI may be needed

Causes

  • Testicular hypogonadism - Klinefelter's syndrome, Mumps
  • Secondary male hypogonadism - Kallmann's syndrome, Haemochromatosis, Prader-Willi syndrome

Management

  • Assess cause
  • Testosterone via im or orally, transdermally or implant for males
  • Treatment with GnRH can help restore fertility with secondary disease

Hirsuitism

  • Causes
    • Polycystic ovary syndrome
    • Congenital adrenal hyperplasia
    • Ovarian tumour or Adrenal tumour
    • ACTH dependent Cushing? s disease

    Clinical

    • Hirsuitism, menstrual problems, acne
    • Virilisation ? male pattern baldness, increase muscle bulk, deep voice, clitoromegaly

    Investigations

    • Elevated testosterone and androstenedione and an elevated DHEAS
    • CT abdomen and pelvis ? Ovarian and adrenal masses

    Management

    • Surgical removal of adrenal or ovarian tumour
    • Oral contraceptive suppresses androgen production
    • Glucorticoids for CAH
    • Spironolactone and Cyproterone acetate
    • Metformin for PCOS
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