parathyroid gland

Parathyroid gland

Anatomy
´ The parathyroids are four endocrine glands(sometimes three or fi ve) about the
size of split peas
´ which usually lie in two pairs behind the lateral lobes of the thyroid gland.
´ The superior parathyroids arise from the fourth branchial pouch and owing to their
short migration can
´ usually be found posterior to the upper two – thirds of the thyroid.
´ The inferior glands arise from the third pouch in association with the developing
Thymus
The inferior parathyroid may lie almost anywhere in the neck or superior mediastinum
although the majority lie within1 cm of the lower thyroid pole.

Physiology

1.It increases the excretion of phosphate from the kidney by inhibiting its tubular
reabsorption (phosphaturic effect); tubular reabsorption of calcium is
reciprocallyincreased.
2 It stimulates osteoclastic activity in the bones,resulting in the decalcifi cation and
liberation
of excessive amounts of calcium and phosphorus in the blood.
3 It activates the 1 α - hydroxylase enzyme in the kidney, which converts the
inactive25 - hydroxycholecalciferol (25 - hydroxy - vitaminD) into 1,25 -
dihydoxycholecalciferol. The resultant activated 1,25 form of vitamin D
facilitates intestinal absorption of calcium
Effects of increased PTH
production
• A raised serum calcium and a lowered serum phosphate, as these substances are
related
reciprocally.
• An increased excretion of phosphate in the urine (phosphaturic effect of PTH).
• An increased excretion of calcium in the urine.The large amount of calcium filtered
(owing to the hypercalcaemia) exceeds the capacity ofthe tubules to reabsorb it all, so
increased calcium excretion occurs.
• Increased osteoclastic activity, with a raised serum alkaline phosphatase associated
withdecalcification of the bones.


´Causes of hypercalcaemia.
´ Endocri 1. Primary hyperparathyroidism 2.Thyrotoxicosis
3.Phaeochromocytoma 4,Adrenal crisis
´ Renal failure Secondary hyperparathyroidism Tertiary
hyperparathyroidism
´ Malignant disease Skeletal secondaries Myeloma
´ Nutritional Milk alkali syndrome Excess vitamin D intake
´ Granulomatous disease Tuberculosis Sarcoidosis
´ Immobilisation
´ Inherited disorders Hypercalciuric hypercalcaemia

Hypoparathyroidism

´ Lack of PTH results in low serum calcium. This leads
initially to paraesthesia (perioral and fi ngertips)then
hyperirritability of skeletal muscle with carp pedal spams.
´ the syndrome being called tetany .
´ The most common cause of this is removal or bruising of
the parathyroids in thyroidectomy
´ Tetany is liable to occur if the serum calcium falls below
1.5 mmol/L.
Clinical feature
´ Spasms may affect any part of the body, but typically the
hands and feet. The wrists flex
and the fingers are drawn together in extension,the so - called
‘ main d ’ accoucheur ’ . This spasm
´ may be induced by placing a tourniquet around the arm for
a few minutes (Trousseau ’ s sign 1 ).
´ Hyperirritability of the facial muscles may be demonstrated
by tapping over the facial nerve,
which results in spasm (Chvostek ’ s sign 2 ).
´ Note that clinical tetany may occur with anormal level of
serum calcium in alkalosis (e.g.
overbreathing, excessive prolonged vomiting)
´ because of a compensatory shift of ionized calcium to the
unionized form in the serum
Hyperparathyroidism
´ There are four distinct types of pathologically increased PTH secretion: primary,
secondary, tertiary and that due to ectopic PTH production by tumours.


Primary hyperparathyroidism
´ The diagnosis of primary hyperparathyroidism is made following the
detection of hypercalcaemia
´ in the presence of inappropriately normal or elevated circulating
PTH levels;
´ the PTH should below if calcium is raised.
´ The hypercalcaemia isusually discovered on routine screening of
patientswho have general symptoms including fatigue,depression
and weakness or less commonly
during the investigation of osteopenia or nephrolithiasis,
´ The annual incidence is highestamong middle - aged and elderly
women (two per1000 population).
Pathology
´ In 85 – 90% of patients, primary hyperparathyroidism is due to a solitary parathyroid
adenoma.
´ The tumours are soft, encapsulated and brownish grey in colour.
´ In 10%of cases, multiglandular hyperplasia is present,
´ which may be associated with multiple endocrine neoplasia (MEN) type I (pancreatic
tumours, pituitary tumours, parathyroid tumours) or
´ may be sporadic or induced by long - term lithium intake.
´ Parathyroid c arcinoma
´ Parathyroid carcinoma is a very rare condition and accounts for less than 1% of all cases of
primary hyperparathyroidism.
´ Patients often have higher serum calcium and PTH levels, and are more likely
´ to have a palpable neck mass than those with benign hyperparathyroidism.
´ Surgery is the only effective treatment.
´ Malignancy should be considered with any gland that is firm, has a grey appearance, or that
isadherent to surrounding structures.
´ If malignancy is confirmed surgery may involve simple excision or en bloc resection,
including excision of local structures such as ipsilateral thyroid, thymus,strap muscles and
recurrent laryngeal nerve.
´ Approximately 30% of tumours will metastasize,
´ but death from the disease is usually attributable to hypercalcaemia, and its effects on the
heart,pancreas and kidney, rather than metastatic tumour burden.
Secondary hyperparathyroidism
´ In some 10% the condition is found to be due to a hyperplasia of all four parathyroid glands.
´ Thisoccurs most commonly in patients with renal failure maintained by dialysis, in whom renal
conversion of 25 - hydroxycholecalciferol (calcidiol) to 1,25 - dihydroxycholecalciferol (calcitriol)
is impaired.
´ This active form of vitamin D is required for absorption of calcium from the gut; defi ciency
results in hypocalcaemia, which chronically stimulates PTH production. The parathyroid glands
undergo hyperplasia in response.
´ To prevent this, dialysis patients are routinely given 1 α -hydroxycholecalciferol (alphacalcidol),
so bypassing renal 1 α - hydroxylase.
´ Tertiary hyperparathyroidism
´ Prolonged secondary hyperparathyroidism leads to autonomous PTH production, which
continues even after renal transplantation replaces the previously deficient renal 1 α -
hydroxylase conversion
´ step. Total parathyroidectomy is required.
Ectopic PTH p roduction
´ Hyperparathyroidism is occasionally due toectopic PTH production by tumours, such as
´ squamous carcinoma of the bronchus.
Clinical features of hyperparathyroidism
´ These depend on the results of excessive production of PTH by the tumour
´ Presenting symptoms may include the following:
• Renal effects : renal stones, infection associatedwith renal calculi, calcifi cation in the renal
substance (nephrocalcinosis) or uraemia.
´ Urinary tract calculi are the most common clinical manifestation of hyperparathyroidism.
´ Bone changes : spontaneous fractures or pain in the bones. X - ray will show decalcifi cation of
the bones with cyst formation
´ Abdominal pain : constipation is common.Dyspepsia or frank duodenal ulceration is also
sometimes associated with parathyroid adenoma, as is pancreatitis
´ Vague ill - health associated with high serum calcium .
´ Cardiovascular : hypertension may be noted at the initial diagnosis and is often associated with
left ventricular hypertrophy.
´ Asymptomatic : an increasing number ofpatients with very few or no symptoms are
now being diagnosed on routine biochemical screening.
´ A careful family history should also be taken to exclude MEN
Investigation
• Serum calcium and PTH . A high serum calcium, corrected for plasma albumin, in
the presence of detectable serum PTH should raise a strong suspicion of primary
hyperparathyroidism. The PTH may be normal or elevated but in either case is
inappropriatelyelevated for the level of serum calcium.
• Serum phosphate may be low (hypophosphataemia) and may
also be present.
• 24 hour urine collection should be taken to exclude familial hypocalciuric hypercalcaemia.
• Serum urea and creatinine should be measured to assess renal function.
• Sestamibi scanning will identify a solitary parathyroid adenoma, and highlight an
ectopic retrosternal location. Sestamibi is technetium - 99 - labellednmethoxy i so b utylisonitrile and,
following injection, is taken up by parathyroid glandsbband retained at 2 hours by adenomas.
Indications for surgery
Indications for parathyroidectomy in primary hyperparathyroidism.
´ Urinary tract calculi
´ Reduced bone density
´ High serum calcium
´ All in younger age group <50 years
´ Deteriorating renal function
´ Symptomatic hypercalcaemia
Surgery
Bilateral neck exploration
Focused parathyroidectomy
´ Complications of parathyroid surgery
1• recurrent laryngeal nerve palsy : occurs in under1% of patients
2. hypocalcaemia : the remaining parathyroid glands are suppressed by the high
PTH levels and may take some time to recover;
3• persistent hypercalcaemia : residual parathyroid tissue remains, possibly a fifth
gland or an ectopic gland within the anterior mediastinum.
´ Recurrent hyperparathyroidism
is diagnosed when hypercalcaemia recurs more than 12 months after an initiallycurative operation. This may occur due to:
• missed pathology at the first operation;
• (rarely) development of a second adenoma;
• hyperplasia in autotransplanted tissue;
• parathyromatosis (disseminated nodules of parathyroid tissue
within the soft tissues of the neck and superior mediastinum
caused by rupture of abnormal parathyroid tissue at initial
surgery).
Reoperative parathyroid surgery is associated with an increased
risk of recurrent laryngeal nerve injury and postoperative hypocalcaemia.


´Management of postoperative
hypocalcaemia
´ Check serum calcium within 24 hours of total thyroidectomy or earlier ifsymptomatic
´ Medical emergency if the level is <1.90 mmol/L: correct
! with 10 mL of 10 per cent calcium gluconate intravenously;
! 10 mL of 10 per cent magnesium sulphate intravenously may also be required
! Give 1 g of oral calcium three or four times daily
! Give 1–3 μg daily of oral 1-alpha-vitamin D if necessary
The s uprarenal g lands
The suprarenal (adrenal) glands are paired glands situated above and medial to the
upper pole each kidney.
The cortex derives from the mesoderm of the urogenital ridge, while the medulla
derives from neural crest ectoderm.
´Physiology
´ Suprarenal cortex
´ The suprarenal cortex secretes three groups of steroids:
1 glucocorticoids , which regulate carbohydrate metabolism, protein breakdown and fat
mobilization;
2 androgenic corticoids , which are virilizing;
3 mineralocorticoids , which regulate mineral and water metabolism. Aldosterone acts to
retain sodium and water and to excrete potassium.
´ Suprarenal medulla
´ The suprarenal medulla is richly innervated with sympathetic preganglionicb fibres,
and produces
" the catecholamines adrenaline (epinephrine) and
" noradrenaline (norepinephrine) in response to autonomic stimulation.
Pathology
The main pathologies are increased function, owing to tumour o rhyperplasia;
decreased function, owing to atrophy, infarction or removal; or abnormal function,
owing to enzyme disorders.
Increased f unction
• Glucocorticoids (Cushing ’ s syndrome):
• Androgenic corticoids : virilism (the adrenogenital syndrome).
• Mineralocorticoids : primary hyperaldosteronism (Conn ’ s syndrome).
• Catecholamines : phaeochromocytoma.
Decreased function
Hypoadrenalism is most commonly a sequel of a
´ prolonged corticosteroid therapy, in which endogenous
steroid production is suppressed, followed by abrupt
steroid withdrawal.
´ • congenital suprarenal hypoplasia;
´ • autoimmune destruction: Addison ’ s disease; 1
´ • suprarenal infarction : a rare consequence of stress or
sepsis (notably meningococcal sepsis);
´ • bilateral adrenalectomy : intentionally (to treat Cushing ’ s
syndrome) or secondary to bilateral nephrectomy;
´ • suprarenal infi ltration by secondary tumours from primaries
in bronchus and breast;
´ • bilateral tuberculosis of the suprarenals
´Incidentaloma
Definition
Incidentaloma is an adrenal mass, detected incidentally by imaging studies
conducted for other reasons, not known previously to have been present or
causing symptoms
´ Prevalence of non-functioning and functioning tumours in
´ patients with incidentalomas. Tumour Prevalence (%)
Non-functioning adenoma 78
Cushing’s adenoma 7
Adrenocortical carcinoma 4
Phaeochromocytoma 4
Myelolipoma 2
Cyst 2
Metastases 2
Conn’s adenoma 1
diagnosis
´ History and clinical examination
´ hormonal assey
´ • morning and midnight plasma cortisol measurements;
´ • a 1-mg overnight dexamethasone suppression test;
´ • 24-hour urinary cortisol excretion;
´ • 12 or 24-hour urinary excretion of metanephrines or plasmafree
metanephrines;
´ • serum potassium, plasma aldosterone and plasma renin activity;
´ • serum DHEAS, testosterone or 17-hydroxyestradiol (virilising or feminising tumour).
´ Computed tomography (CT) or magnetic resonance imaging (MRI) should
be performed in all patients with adrenal masses.
´ biopsy
"Cushing ’ s syndrome
" Cushing ’ s syndrome 2 is produced by increased circulating corticosteroids.
" Excepting therapeutic exogenous steroid administration, the majority of cases result from a pituitary
adenoma producing ACTH, resulting in hyperplasia of the suprarenal cortex
" The syndrome usually affects young adults
" women more often than men.
Clinical features of Cushing’s syndrome
Weight gain/central obesity
Diabetes
Hirsutism
Hypertension
Skin changes (abdominal striae, facial plethora,ecchymosis, acne)
Muscle weakness
Menstrual irregularity/impotence
Depression/mania
Osteoporosis
Hypokalaemia
Diagnosis
• Morning and midnight plasma cortisol levels are elevated,possibly with loss of diurnal
rhythm.
• Dexamethasone fails to suppress 24-hour urinary cortisol excretion.
• Serum ACTH levels discriminate ACTH-dependent from ACTH-independent disease.
´ Elevated or normal ACTH levels provide evidence for an ACTH-producing pituitary
tumour (85 per cent) or ectopic ACTH production.
´ Therefore, in patients with elevated ACTH, MRI of the pituitary gland must be
performed.
Treatment:
´Medical therapy with metyrapone or ketoconazole reduces steroid
synthesis and secretion and can be used :
´ to prepare patients with severe hypercortisolism preoperatively or
´ if surgery is not possible.
´ ACTH-producing pituitary tumours are treated by trans-sphenoidal
resection or radiotherapy.
´ If an ectopic ACTH source is localised, resection will correct
hypercortisolism.
´ A unilateral adenoma is treated. by adrenalectomy
´ In cases of bilateral ACTH-independent disease bilateral
adrenalectomy is the primary treatment.
Preoperative management
Patients with Cushing’s syndrome are at an increased risk of hospitalacquired
infection, thromboembolic and myocardial complications.
Therefore, prophylactic anticoagulation and the use of
prophylactic antibiotics are essential
Postoperative management
After unilateral adrenalectomy supplemental cortisol should be given postoperatively because the
contralateral gland willbe suppressed.
In total, 15 mg/hour is required parenterally for the first 12 hours followed by a daily dose of 100
mg for 3 days,which is gradually reduced thereafter.
After unilateral adrenalectomy,the contralateral suppressed gland needs up to one year
to recover adequate function.
Primary hyperaldosteronism(Conn’s syndrome)
Conn ’ s syndrome 3 is a rare syndrome produced by an aldosterone - secreting adenoma of the
suprarenalcortex.
Characteristically, there is a low serum potassium.
Clinical features
" Most patients are between 30 and 50 years of age
" with a femalepredominance.
" Apart from hypertension, patients complain of
" non-specific symptoms: headache, muscle weakness, cramps,intermittent paralysis, polyuria,
polydypsia and nocturia
" Special i nvestigations
• Serum electrolytes : hypernatraemia and hypokalaemia.
• Plasma aldosterone : the diagnosis is confi rmed by demonstration of excess aldosterone in the
plasma.
• Abdominal CT may demonstrate the tumour, which is often small.
• Selective angiography and selective venous sampling from the suprarenal veins with
aldosterone estimations may be needed to delineate the lesion.
Treatment
1. The first-line therapy for PHA with bilateral hyperplasia is medical
treatment with spironolactone.
In most cases supplemental antihypertensive medication is necessary.
2.Unilateral laparoscopic adrenalectomy is an effective therapy in
patients with clear evidence of unilateral or asymmetrical bilateral disease
3. A subtotal resection can be considered in thecase of a typical single
Conn’s adenoma.
4. In 10–30 per cent of patients who undergo an adrenalectomy,
treatment,
treatment,
hypertension persists despite adequate diagnostic work-up and