Hypoparathyroidism

Hypoparathyroidism is a condition of reduced or absent PTH secretion, resulting in hypocalcaemia and hyperphosphataemia. It is far less common than hyperparathyroidism.

The causes of hypoparathyroidism are:
- Removal or damage of the parathyroid glands during thyroidectomy—most common cause of hypoparathyroidism resulting from inadvertent damage or removal.
- Autoimmune parathyroid disease—usually occurs in patients who have another autoimmune endocrine disease, e.g. Addison’s disease (autoimmune endocrine syndrome type 1).
- Congenital deficiency (DiGeorge syndrome)— rare, congenital disorder caused by arrested development of the third and fourth branchial arches, resulting in an almost complete absence of the thymus and parathyroid gland.

The effects of hypoparathyroidism are:
- ↓ release of Ca²⁺ from bones. 
- ↓ Ca²⁺ reabsorption but ↑ PO ₄³⁻ re absorption by the kidneys
- ↓ 1-hydroxylation of 25-hydroxyvitamin D by kidney.

Most symptoms of hypoparathyroidism are those of hypocalcaemia:
- Tetany—muscular spasm provoked by lowered plasma Ca 2+ 
- Convulsions.
- Paraesthesiae.
- Psychiatric disturbances, e.g. depression, confusional state and even psychosis.
- Rarely—cataracts, parkinsonian-like movement disorders, alopecia, brittle nails.

Management is by treatment with large doses of oral vitamin D; the acute phase requires intravenous calcium and calcitriol (1,25-dihydroxycholecalciferol, i.e.  activated vitamin D).

Fibrous and Fibro-Osseous Tumors

Fibrous tumors of bone are common and comprise several morphological variants.
1. Fibrous Cortical Defect and Nonossifying Fibroma 
Fibrous cortical defects occur in 30% to 50% of all children older than 2 years of age; they are probably developmental rather than true neoplasms. The vast majority are smaller than 0.5 cm and arise in the metaphysis of the distal femur or proximal tibia; almost half are bilateral or multiple. They may enlarge in size (5-6 cm) to form nonossifying fibromas. Both lesions present as sharply demarcated radiolucencies surrounded by a thin zone of sclerosis. Microscopically are cellular and composed of benign fibroblasts and macrophages, including multinucleated forms. The fibroblasts classically exhibit a storiform pattern. Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions. Most undergo spontaneous differentiation into normal cortical bone. The few that enlarge into nonossifying fibromas can present with pathologic fracture; in such cases biopsy is necessary to rule out other tumors.

2. Fibrous Dysplasia 

is a benign mass lesion in which all components of normal bone are present, but they fail to differentiate into mature structures. Fibrous dysplasia occurs as one of three clinical patterns:
A. Involvement of a single bone (monostotic)
B. nvolvement of multiple bones (polyostotic)
C. Polyostotic disease, associated with café au lait skin pigmentations and endocrine abnormalities, especially precocious puberty (Albright syndrome).

Monostotic fibrous dysplasia accounts for 70% of cases. It usually begins in early adolescence, and ceases with epiphyseal closure. It frequently involves ribs, femur, tibia & jawbones. Lesions are asymptomatic and usually discovered incidentally. However, fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the face or skull is involved, disfigurement can occur.

Polyostotic fibrous dysplasia without endocrine dysfunction accounts for the majority of the remaining cases. 
It tends to involve the shoulder and pelvic girdles, resulting in severe deformities and spontaneous fractures.

Albright syndrome accounts for 3% of all cases. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large, dark to light brown (café au lait), and irregular.

Gross features

• The lesion is well-circumscribed, intramedullary; large masses expand and distort the bone.
On section it is tan-white and gritty.

Microscopic features

• There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming
• The above are set within fibroblastic proliferation
Individuals with monostotic disease usually have minimal symptoms. By x-ray, lesions exhibit a characteristic ground-glass appearance with well-defined margins. Polyostotic involvement is frequently associated with progressive disease, and more severe skeletal complications (e.g., fractures, long bone deformities, and craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapy. 

Pulmonary embolism

A pulmonary embolism (thromboembolism) occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.

Clinical presentation

Signs of PE are sudden-onset dyspnea (shortness of breath, 73%), tachypnea (rapid breathing, 70%), chest pain of "pleuritic" nature (worsened by breathing, 66%), cough (37%), hemoptysis (coughing up blood, 13%), and in severe cases, cyanosis, tachycardia (rapid heart rate), hypotension, shock, loss of consciousness, and death. Although most cases have no clinical evidence of deep venous thrombosis in the legs, findings that indicate this may aid in the diagnosis.

Diagnosis

The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography

An electrocardiogram may show signs of right heart strain or acute cor pulmonale in cases of large PEs

In massive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure.

Treatment

Acutely, supportive treatments, such as oxygen or analgesia

In most cases, anticoagulant therapy is the mainstay of treatment. Heparin or low molecular weight heparins are administered initially, while warfarin therapy is given

Pemphigus
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against hemidemosomal attachment of epidermis cells.
3. Histologically characterized by acantholysis, in which epidermal cells appear to detach and separate from each other, as seen by Tzanck smears.
4. Can be life-threatening if untreated.
5. A positive Nikolsky sign is observed.
Because of sloughing of the epidermis, a red blister forms after pressure is applied to affected skin.
6. Treatment: corticosteroids.

Hypopituitarism

Hypopituitarism is caused by

1. Loss of the anterior pituitary parenchyma
    a. congenital 
    b. acquired  
    
2. Disorders of the hypothalamus e.g. tumors; these interfere with the delivery of pituitary hormone-releasing factors from the hypothalamus.  

Most cases of anterior pituitary hypofunction are caused by the following:
1. Nonfunctioning pituitary adenomas 
2. Ischemic necrosis of the anterior pituitary is an important cause of pituitary insufficiency. This requires destruction of 75% of the anterior pituitary. 

Causes include  

a. Sheehan syndrome, refers to postpartum necrosis of the anterior pituitary, and is the most cause. During pregnancy the anterior pituitary enlarges considerably because of an increase in the size and number of prolactin-secreting cells. However, this physiologic enlargement of the gland is not accompanied by an increase in blood supply. The enlarged gland is therefore vulnerable to ischemic injury, especially in women who develop significant hemorrhage and hypotension during the peripartum period. The posterior pituitary is usually not affected. 

b. Disseminated intravascular coagulation 
c. Sickle cell anemia 
d. Elevated intracranial pressure 
e. Traumatic injury
f. Shock states

3. Iatrogenic i.e.  surgical removal or radiation-induced destruction
4. Inflammatory lesions such as sarcoidosis or tuberculosis
5. Metastatic neoplasms involving the pituitary. 
6. Mutations affecting the pituitary transcription factor Pit-1 

Children can develop growth failure (pituitary dwarfism) as a result of growth hormone deficiency.

Gonadotropin or gonadotropin-releasing hormone (GnRH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men. TSH and ACTH deficiencies result in symptoms of hypothyroidism and hypoadrenalism. Prolactin deficiency results in failure of postpartum lactation. 

Megaloblastic anaemia

Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-

Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum  and jejunum

Causes of deficiency .-

- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)

Features:

(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).

Blood picture :

- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and  basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.

Bone marrow:

- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
 -Giant stab forms (giant metamyelocytes).