ANAEMIA
Definition. Reduction of the hemoglobin level below the normal for the age and sex of the patient

Classification
1. Blood loss anaemia:
- Acute.
- Chronic (results in iron deficiency).

2. Deficiency anaemia:

- Iron deficiency.
- Megaloblastic anaemia-BI2 and Folic acid deficiency.
- Protein deficiency.
- Scurvy-Vitamin C deficiency.

3. Marrow dysfunction:
- Aplastic anaemia.
- Marrow infiltration.
- Liver failure.
- Renal failure.
- Collagen diseases.

4 Increased destruction (Heamolysis)
- Due to corpuscular defects.
- Due to extra corpuscular defects
 

Multiple Endocrine Neoplasia Syndromes (MEN)

The MEN syndromes are a group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas, and carcinomas) of multiple endocrine organs. Even in one organ, the tumors are often multifocal. These tumors are usually more aggressive and recur in a higher proportion of cases than similar but sporadic endocrine tumors. 

Multiple Endocrine Neoplasia Type 1 (MEN1) is inherited in an autosomal dominant pattern. The gene (MEN1) is a tumor suppressor gene; thus, inactivation of both alleles of the gene is believed to be the basis of tumorigenesis. Organs commonly involved include the parathyroid, pancreas, and pituitary (the 3 Ps). Parathyroid hyperplasia is the most consistent feature of MEN-1 but endocrine tumors of the pancreas are the leading cause of death because such tumors are usually aggressive and present with metastatic disease.

Zollinger-Ellison syndrome, associated with gastrinomas, and hypoglycemia, related to insulinomas, are common endocrine manifestations. Prolactin-secreting macroadenoma is the most frequent pituitary tumor in MEN-1 patients. 

Multiple Endocrine Neoplasia Type 2 (MEN2)

MEN type 2 is actually two distinct groups of disorders that are unified by the occurrence of activating mutations of the RET protooncogene. Both are inherited in an autosomal dominant pattern. 

MEN 2A

Organs commonly involved include:

Medullary carcinoma of the thyroid develops in virtually all cases, and the tumors usually occur in the first 2 decades of life. The tumors are commonly multifocal, and foci of C-cell hyperplasia can be found in the adjacent thyroid. Adrenal pheochromocytomas develop in 50% of patients; fortunately, no more than 10% are malignant. Parathyroid gland hyperplasia with primary hyperparathyroidism occurs in a third of patients. 

Multiple Endocrine Neoplasia, Type 2B 

Organs commonly involved include the thyroid and adrenal medulla. The spectrum of thyroid and adrenal medullary disease is similar to that in MEN-2A. However, unlike MEN-2A, patients with MEN-2B: 

1. Do not develop primary hyperparathyroidism
2. Develop extraendocrine manifestations: ganglioneuromas of mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid habitus 

Congestive heart failure (CHF)
A. Left-sided CHF

1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.

B. Right-sided CHF

1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.

ADRENAL INSUFFICIENCY

Adrenocortical hypofunction is either primary (adrenocrtical) or secondary (ACTH deficiency). Primary insufficiency is divided into acute & chronic. 
Acute Adrenocortical Insufficiency occurs most commonly in the following clinical settings
- massive adrenal hemorrhage including  Waterhouse-Friderichsen syndrome 
- Sudden withdrawal of long-term corticosteroid therapy
- Stress in those with chronic adrenal insufficiency 

Massive adrenal hemorrhage may destroy the adrenal cortex sufficiently to cause acute adrenocortical 
insufficiency. This condition may occur 
1. in patients maintained on anticoagulant therapy 
2. in postoperative patients who develop DIC
3. during pregnancy 
4. in patients suffering from overwhelming sepsis (Waterhouse-Friderichsen syndrome) 

Waterhouse-Friderichsen syndrome is a catastrophic syndrome classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms, including Pseudomonas species, pneumococci & Haemophilus influenzae. The pathogenesis of the syndrome remains unclear, but probably involves endotoxin-induced vascular injury with associated DIC.

Chronic adrenocortical insufficiency (Addison disease) results from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders: 
1. autoimmune adrenalitis (the most common cause; 70% of cases) 
2. tuberculosis &fungal infections 
3. AIDS
4. Metastatic cancers   
In such primary diseases, there is hyperpigmentation of the skin oral mucosa due to high levels of MSH (associated with high levels of ACTH).

Autoimmune adrenalitis is due to autoimmune destruction of steroid-producing cells. It is either isolated associated other autoimmune diseases, such as Hashimoto disease, pernicious anemia, etc. 

Infections, particularly tuberculous and fungal

Tuberculous adrenalitis, which once was responsible for as many as 90% of cases of Addison disease, has become less common with the advent of antituberculous therapy. When present, tuberculous adrenalitis is usually associated with active infection elsewhere, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum is the main cause. 

AIDS patients are at risk for developing adrenal insufficiency from several infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications.
 
Metastatic neoplasms: the adrenals are a fairly common site for metastases in persons with disseminated carcinomas. Although adrenal function is preserved in most such patients, the metastatic growths sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the major primary sources. 

Secondary Adrenocortical Insufficiency

Any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH leads to a syndrome of hypoadrenalism having many similarities to Addison disease. In such secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low. 

Secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration. 

Pathological features of adrenocortical deficiency 

- The appearance of the adrenal glands varies with the cause of the insufficiency. 
- In secondary hypoadrenalism the adrenals are reduced to small, uniform, thin rim of atrophic yellow cortex that surrounds a central, intact medulla. Histologically, there is atrophy of cortical cells with loss of cytoplasmic lipid, particularly in the zonae fasciculata and reticularis. 
- In primary autoimmune adrenalitis there is also atrophy of the cortex associated with a variable lymphoid infiltrate that may extend into the subjacent medulla. The medulla is otherwise normal.  
- In tuberculosis or fungal diseases there is granulomatous inflammatory reaction. Demonstration of the responsible organism may require the use of special stains.  
- With metastatic carcinoma, the adrenals are enlarged and their normal architecture is obscured by the infiltrating neoplasm.  
 

Vitiligo is an autoimmune destruction of melanocytes resulting in areas of depigmentation.
 - commonly associated with other autoimmune diseases such as pernicious anemia, Addison's disease, and thyroid disease.
 - common in the Black population

Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
 - due to Pitysporium species
 - can be seen in AIDS as an opportunistic infection