Hypo Parathyroid Ism

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A 30-year old male admitted with headache and generalized convulsions. His medical history is notable only for

thyroidectomy four years back . Fundi examination foundsB/L papilloedema and no focal neurological sign.Trousseau s sign is positive. BMI is 27 kg/ m 2. ECG shows QT interval of >50% of R-R interval. His total serum calcium is1.7 mmol/l. CT brain ( non contrast and contrast) is normal.

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Hypoparathyroidism

Dr.Upul Pathirana

Registrar (Medicine)

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Control of Mineral Metabolism by Parathyroid Hormone

Low serum Ca 2+sensed throughCaSRs

Parathyroidglands

Intestine

Bone

Kidney

Boneresorption

Increasedcalciumreabsorption,decreased

PO 4reabsorption

Increased Ca 2+and PO4into serum(normal rangerestored)

PTH

1 ,25 (OH)2D25 (OH)D

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W hen the actions of PTH are reduced or lost

Hypocalcemia

Hyperphosphatemia,

Hypercalciuria

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The Clinical Problem

Hypocalcemia

defined as low serum levels of albumin-corrected total calcium(normal range, 8. 5 to 10 .5 mg per deciliter [ 2 .1 to 2 .6 mmolper liter]) or of ionized calcium

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Hypocalcemia

Viewed broadly inadequate parathyroid hormone (PTH) secretion or

receptor activation

insufficient supply of vitamin D or activity of thevitamin D receptor

abnormal magnesium metabolism

clinical situations in which multiple factors (e.g.,pancreatitis, sepsis, and critical illness)

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Presentation

Neuromuscular symptoms are typically the most prominent muscle cramping, twitching, and spasms circumoral and acral numbness and paresthesias laryngospasm; bronchospasm seizures

Two signs Chvosteks sign Trousseau s sign

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Severe hypocalcaemia

Cardiac function may beaffected, manifested by

prolonged QT interval

corrected for heart rate (QTc)

in rare cases, depressedsystolic function and heartfailure

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Pseudortumor cerebri

Marked papilloedema

Neither a mass nor an increase in ventricular size

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Pseudotumor cerebri

Modified Dandy criteria

1 Symptoms of raised intracranial pressure (headache, nausea, vomiting,transient visual obscurations, or papilledema)

2 No localizing signs with the exception of abducens (sixth) nerve palsy

3 The patient is awake and alert

4 Normal CT / MRI findings without evidence of thrombosis

5 LP opening pressure of > 25 cmH 2O and normal biochemical andcytological composition of CSF

6 No other explanation for the raised intracranial pressure

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Hypoparathyroidism can be congenital or acquired

Acquired hypoparathyroidism is most commonly the

result of inadvertent removal or irreversible damage tothe glands, usually to their blood supply, duringthyroidectomy, parathyroidectomy, or radical neckdissection

Immune-mediated destruction of the parathyroid glandscan be either isolated or part of autoimmunepolyendocrine syndrome type 1 (APS-1)

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Hypoparathyroidism -Differential Diagnosis


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Hypoparathyroidism may also be caused by accumulation inthe parathyroid glands of iron (hemochromatosis or

transfusion-dependent thalassemia) or copper (W

ilson sdisease)or (in rare cases) by iodine- 131 therapy for thyroiddiseases or metastatic infiltration of the parathyroid glands bytumor

Magnesium depletion or excess may cause hypocalcemia byinducing functional hypoparathyroidism

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G enetic disorders must also be considered as a possible causeof hypocalcemia. (Di G eorge or velocardiofacial syndrome)

Inherited hypoparathyroidism and are manifested asautosomal dominant hypocalcemia at any age

Familial hypoparathyroidism due to dysgenesis of theparathyroid glands

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1 . Postsurgicalhypoparathyroidism

2 . Autoimmunehypoparathyroidism

3. Deposition of heavy metalsin parathyroid tissue

4. Radiation-induceddestruction of parathyroidtissue

5 . Metastatic infiltration of theparathyroid glands

6. Magnesium depletion orexcess

7. G enetic disorders / Inheritedhypoparathyroidism

8. Pseudohypoparathyroidism

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DiG eorge syndrome

Familial condition in which the hypoparathyroidism isassociated with

Intelectual impairment Cataract Calcified basal ganglia Occasionaly with specific autoimmune disease and

immune deficiencies

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Pseudohypoparathyroidism

Syndrome of end-organ resistance to PTH ,it isassociated with

Short stature Short metacarpals Subcutaneous calcifications Intelectual impairment

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Pseudo-pseudohypoparathyroidism

Phenotypic defects but without any abnormalities of calcium metabolism

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Evaluation

Review of the patient s medical and family histories

A history of neck surgery

A family history of hypocalcemia (genetic cause)

autoimmune endocrinopathies (e.g., adrenal insufficiency) orcandidiasis prompts consideration of autoimmunepolyendocrine syndrome type 1 .

Immunodeficiency and other congenital defects point to theDiG eorge syndrome

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Evaluation

Physical examination

neuromuscular irritability by testing for Chvostek s andTrousseau s signs

skin should be examined carefully for a neck scar (whichsuggests a postsurgical cause of hypocalcemia); for candidiasisand vitiligo (which are suggestive of APS- 1); and for generalizedbronzing and signs of liver disease (which are suggestive of

hemochromatosis)

Features such as growth failure, congenital anomalies, hearingloss, or retardation point to the possibility of genetic d isease

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Pseudohypoparathyroidism

Patients with pseudohypoparathyroidism have alaboratory profile that resembles that in patientswith hypoparathyroidism

(i.e., low calcium and high phosphorus levels),

but they have elevated PTH levels

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Vitamin D deficiency

In classic vitamin D deficiency,

intact PTH levels are elevated,serum phosphorus levels are low or at the lowend of the normal range

(in marked contrast to the high levels in

hypoparathyroidism)

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Treatment and Clinical Monitoring1 .Calcium therapy

The goals of therapy are to control symptoms while minimizingcomplications

Urgent care of patients with hypocalcemia should be guided by thenature and severity of the symptoms and the level of serum calcium

Severe symptoms (e.g., seizures, laryngospasm, bronchospasm, cardiacfailure, and altered mental status) warrant intravenous calcium

therapy, even if the serum calcium level is only mildly reduced (e.g.,7.0 to 8. 0 mg per deciliter [ 1 .75 to 2 .00 mmol per liter])

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Intravenous infusions are generally tapered slowly (over a period of 24to 48 hours or longer) while oral therapy is adjusted

Oral therapy is appropriate in patients with mildly reduced serum totalcalcium levels (7. 5 to 8. 0 mg per deciliter [ 1 .87 to 2 .00 mmol perliter]) who have symptoms, even if they are nonspecific ones (e.g.,fatigue, anxiety, and reduced well-being) because these symptomsmay improve with treatment

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Treatment and Clinical Monitoring


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Vitamin D metabolites and analogues are essential to the managementof hypoparathyroidism . The key complication to avoid is vitamin Dintoxication (hypercalcemia and hypercalciuria) with its adverseeffects on the renal and central nervous systems

Calcitriol is preferred (over vitamin D 2 or D3) because of its potencyand rapid onset and offset of action

Thiazide diuretics can be used to reduce (or prevent) hypercalciuriacaused by calcium and vitamin D therapy

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Treatment and Clinical Monitoring2 . Vitamin D therapy


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Treatment and Clinical Monitoring3.reduce hyperphosphataemia

Hyperphosphatemia may be addressed by minimizing thepatient s dietary intake of phosphate (e.g., in meats, eggs,

dairy products, and cola beverages) and,

If needed, with phosphate binders to control or prevent anunacceptable calcium phosphate product

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Follow up

Levels of serum calcium, phosphorus, and creatinine should bemeasured weekly to monthly during initial dose adjustments,

with twice-yearly measurements once the regimen has beenStabilized

Urinary calcium and creatinine levels are measured twice yearlyto detect any renal toxic effects of hypercalciuria

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The goals of therapy are symptom control, a serum albumincorrected total calcium level at the lower end of the normalrange (approximately 8. 0 to 8. 5 mg per deciliter [ 2 .00 to 2 .12 mmol per liter]), a 24- hour urinary calcium level well below300 mg, and a calcium phosphate product below 55

Annual slit-lamp and ophthalmoscopic examinations arerecommended to monitor for the development of cataracts inall patients

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Follow up


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???

There are no available data from clinical trials to show thatcomplications of chronic hypocalcemia are preventable with

aggressive therapy or that patients with mildly abnormalbiochemical findings derive benefits from therapy.

Clinical experience, however, indicates that patients with serumcalcium levels near the lower end of the normal range tend tofeel better, with less tetany, muscle cramps, and fatigue, thanthose with mild hypocalcemia who are not treat

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Areas of Uncertainty

Hypoparathyroidism is one of the few endocrinopathies for whichhormone-replacement therapy is not readily available

Only a few small, randomized trials have assessed the use of injectablehuman PTH in patients with this condition

Limited data suggest that the quality of life may be compromised inpatients with hypoparathyroidism despite treatment to optimize

their biochemical values

The effect of PTH replacement on quality-of-life measures is notknown.

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G uidelines

There are no formal guidelines for the management of hypoparathyroidism

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Conclusions and Recommendations

The initial evaluation of a patient withhypocalcemia should include adetailed family history (which may suggest a genetic cause) andrelevant medical history (particularly regarding neck surgery andautoimmune disease).

Laboratory testing should include measurements of serum total andionized calcium, albumin, phosphorus, magnesium, and intact PTHlevels

If the patient has severe symptoms, therapy with intravenous calciumshould be initiated immediately, and the diagnosis pursued afterthe patient s condition has been stabilized

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Reference

The new england journal of medicine

( N Engl J Med 200 8;3 59: 391 -403)

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Thank You

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Hypo Parathyroid Ism

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