5.DISORDERS  AND/ OR ADVERSE REACTIONS-  HORMONES -SUMMARY

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1.Evidence Based Medicine                                                                                                  i.Premenstrual sydrome (PMS)

2.Facts on Finger Tips                                                                                                            i. Hydatidiform  Mole                                                                                                          ii.Menorrhagia                                                                                                                    iii. Polycystic Ovary Syndrome                                                                                        iv. Endometriosis                                                                                                                v. Diagnosing Diabetes Mellitus                                                                                        vi. Grave's Disease

3. Disorders and/or Adverse Reactions                                                                                Item 1 to 16

                       EVIDENCE BASED MEDICINE (April 2003)

FACTS ON FINGER TIPS

3. MENORRHAGIA

Salient Features (MIMS)

 Definition 

1.Excessive menstrual blood loss, objectively defined as more than 80ml per cycle      2.A more practical definition for use in family practice is ‘disproportionate menstrual            losses occurring over several consecutive cycles’.

Epidemiology 

1. A very common problem                                                                                           2.But about 25 per cent of women who complain of heavy periods have ‘normal’ blood       loss.

Clinical features 

1. History of bleeding that cannot be controlled with a single tampon or sanitary towel.   2.Waking at night to change tampon or towel.                                                       3.Regularly passing ‘clots’ or ‘flooding’.                                                                   4.Crampy uterine pain may be a feature

Investigations 

1.Patients should keep a menstrual diary of symptoms                                               2.Full blood counts and thyroid function tests.                                                     3.Ultrasound scan if fibroids suspected

Management 

1.Refer over -40s for further investigations                                                        2.Combined oral contraceptive should be prescribed if contraception is also required 3.NSAIDs such as mefenamic acid reduce loss by 20-50 per cent if taken during                 menstruation                                                                                                           .   4.Tranexamic acid reduces blood loss by up to 70 per cent, but has side effects             5. Surgical options are mainly reserved for those who fail to respond to medical                 treatment

Key Points 

1.Consider the possibility of endometrial cancer                                                      2.Women taking danazol must avoid becoming pregnant

5.DISORDERS  AND/OR ADVERSE REACTIONS- HORMONES - SUMMARY

  ( Ref- Harrisons - Priniciples of Internal Medicine Ninth Edition )

1. Cholestatic jaundice  ( 209 )
2. Hepatocellular disorders ( 209 )
3. Hepatomegaly ( 209 )
4. Ascites ( 211 )
5. Disorders of thyroid  (1694)
6. Addisonian -like syndrome ( 1728 )
7. Gynaecomastia ( 1789 )
8. Galactorrhea - ( 1787 )
9. Sexual dysfunction ( 386 )
10.Gaucher disease ( 525)
11.Fabry disease - (525)
12. Pompe Disease- (527)
13.Homocystinurias (463)
14. Cystinosis ( 469)
15. Muccopolysaccharidoses -MPS ( 526)
16.  Wilsons disease- (491)

1.Cholestatic jaundice  ( 209 )

Obstructive or cholestatic jaundice, by this is meant that clinically and especially biochemically there is little to suggest hepatocellular damage and that the the main features point to interference  with or obstruction in, the flow of bile.
Typically one would expect such a patient to show
1. predominantly conjugated hyperbilirubinemia
2. minimal biochemical changes of parenchymal liver damage
3. a moderate to a marked increase in the serum alkaline phophatase level

2. Hepatocellular disorders ( 209 )

Hepatacellular disoders in which jaundice associated with obstructive or cholestatic , phase occurs,
1. occassional cases of viral hepatitis,
2. drug reactions, especially those due to chlorpromazine and methyltestosterone
3. some cases of alcoholic hepatitis or alcohol- induced hepatitis or fatty liver,
4. jaundice in the last trimester or pregnancy
5. most cases of Dubin- Johnson or Rotor syndrome
6. benign recurrent intrahepatic cholestasis and
7. certain types of postoperative jaundice 

3. Hepatomegaly ( 209 )

In the supine position, the major part of liver lies beneath the right rib cage. In some normal
persons the  liver edge may be palpable 1 to 2 cm below the right costal margin and palpable liver edge by itself does not necessarilty indicate hepatomegaly

4. Ascites ( 211 )

Often the ascites is a component or complication of cirrhosis, congestive heart failure, nephrosis or disseminated carcinomatosis, However, even when the cause seems obivous, it is often important to detremine whether another separate or related diseases process has supervened

5. Disorders of thyroid  ( 1694)

The normal function of the thyroid gland is to secrete L-thyroxine T4 and  3,4,5 triodod-L-throonine T3 iodinated amino acids that are active thyroid hormones and that influences a deversity of metabolic processes. Insufficient hormone secretion results in in the syndrome of hypothyroidism or myxedema in which decreased oxugen consumption hypometabolism) is a classic manefestation. Convesely excessive secretion of active hormone results in hypermetabolism and other features of a syndrome termed hyperthroidism or throtoxicosis. 

Adverse Reaction- drugs
 1. Oral contraceptives
 2. Bromosulphalein
 3. Phenindione
 4. Iodides
 5. Tolbutamide
 6. Chlorpropamide
 7. Lithium
 8. Acetazolamide
 9. Gold salts
 10. Dimercaprol
 11. Clofibrate
 12. Phenothiazine ( long term )
 13. Phenylbutazone
 14. Sulfonamides
 15. Phenytoin

6. Addisonian -like syndrome ( 1728 )

This disorder is also called Addisons  disease or chronic glucocortoid deficiency. Addisons
description, namely  - general langour and debility, remarkable feebleness of the heats action ,irritability of the stomach, and a peculiar change of the color f the skin, summarizes the dominant clinical features of the disease 

 Adverse reactions - drugs ( 386 )
  1. Busulfan

7. Gynaecomastia ( 1789 )

Under usual conditions no breast is palpable in the normal adult man. However, enlargement  of male  breast can either occur as a manifestation of normal physiological development at certain stages of life or as as the result of a variety of pathological conditions. In gyneacomastia due to either to normal or abnormal cause the enlargement is believed to result from disturbances of normal ratio of active androgen to estrogen in plasma or within the breast itself.

 Adverse reactions - drug ( 386 )
  1. Estrogens
  2. Testosteronone
  3. Spironolactone
  4. Digitalis
  5. Reserpine
  6. Methyldopa
  7. Isoniazid
  8. Ethionamide
  9. Griseofluvin
 
8. Galactorrhea - ( 1787 )

Exactly what constitutes nonpuerperal or inappropiate lactation is not always clearly defined in the literature. According to studies of Friedman and Goldfien , it is not possible to  demonstate any  breast secretion whatosoever in normal regularly menstruating women, but breast secretions may  be present in as many as one-fourth of normal women who have been pregnant in the past and may be of no clinical significance in these instances.

  Adverse reactions - drug ( 386 )
  1. Methyldopa
  2. Phenothiazine
  3. Reserpine  
  4. Tricyclic antidepressants
  5. Dexamphetamine

9. Sexual dysfunction ( 1810)

Sexual disorders could be due to various factors eg. Some sexual disorders are manifestations of mental disorders and will respond only to treatement of mental illness. Diminished sexual responsiveness , impotence, or ejaculatory disturbances may be indication of depression. Bizzare sexual complaints with increased or decreased sexual activity can indicate incipent psychosis. Hypersensuality can occur with the onset of mania. 

Alcohol may play a significant role in potency disturbances. Barbiturates and opiates also cause reduced libido and impotence. Antihypertensive agents, tranquilizers, hynotics, analgesics  and sedatives all may influence sexual function in the male.

 a.Impaired ejaculation
  Adverse reaction - drug
   1. Guanethidine
   2. Derisoquin
   3. Betaanidine
   4. Thioridazine

b. Decreased libido and impotence
   1. oral contraceptives
   2. Sedatives
   3. Major tranquiliozers
   4. Lithium
   5. Methyldopa
   6. Clonidine

10.Gaucher disease ( 525)

     Gaucher disease is characterized by functional deficiency in beta-glucocerebrosidase enzymatic  activity and the resultant accumulation of  lipid glucocerbroside in the tissue macrophanges,  which becomes engroged and are termed as Gaucher cells.

11.Fabry disease - (525)
  
 Fabry Disease is an X-linked genetic disorder of glycosphingolid metabolism. 
 Defeciency of the glycosomal enzyme alpha-galatosidase A leads to progressive accumulation  of glycosphingolipids  predominantly GL-3 in many  body tissues , occuring over a period of  years or decades.
 
12. Pompe Disease- (527)
      Glycogen storage type II (Pompe disease) is  the prototype lysomal storage diseases.
      It  is an inherited  disorder of glycogen metabolism caused by the absence of marked
      deficiency of the lyosomal  enzyme acid glucosidase.

13.Homocystinurias (463)
     Homocystinurias are three biochemically  and clinically distinct disorders each                       characterized  by increased  concentration of sulfur-containg amino acid , homocysteine       in blood and urine.  The most common form results from markedly reduced catalying a          key step in transsulfuration  pathway by which methionine is converted to cysteine.

     Depending on the underlying disorder , some patients with each of the homocysteinuria        show  chemical and in some instances clinical improvement  following adminstration of        specific  improvements following administreration of specific vitamin supplements                 (pyrodoxine, folate,  or cobalamin

14. Cystinosis ( 469)
      Cystinosis  is rare disorder characterrized by the introsomal accumulation of free                  cystine in  body tissue. This results in apperarance of cystine crystals in cornea,                     conjuctivitis, bone marrow,  lymph nodes, leukocytes and internal organs.

      These clinical forms have been identified - an infantile ( nephropathic ) form leading to t          the  Fancomi syndrome and renal insufficiency in the first decade,  juvenile                             (intermediate)  form   in which the renal disease becomes manifest during the second          decade, and an adult ( benign)   form  charaterized  by deposition of cystine in the                  cornea but not in the kidney.

15. Muccopolysaccharidoses -MPS ( 526)
      The mucoploysaccharidosis represent  a broad spectrum of disorders due to deficiency       of  one group of enzymes which degrade three classes of mucolpolysaccharides -               heparin sulfate,  dermatan sulfate, and keratin sulfate. The general MPS  phenotype               includes  coarse facies, corneal clouding, hepatosplenomegaly , joint stiffness, hernias,        dysotosis mutiplex, mucopolysacharide excretion in the urine and metachromatic                  staining in peripheral leukocytes  and bone marrow.   

16.  Wilsons disease- (491)
       Wilsons disease  hepatolenticular degeneration ) is an inherited metabolic defect                   resulting in  excess copper accumulation, possibly because the liver lacks the                       mechanism to extract free copper into the bile.
        Hepatocytes store excess copper , but when their capacity is exceeded , copper is                released  into the blood and taken into extrahepatic sites.

       Treat this condition with a low copper diet and chelating agents that bind copper to                 facilitate  its excretion from the body. Trientine is a chelating compound for removal of           excess copper  from the body. 

FACTS ON FINGER TIPS

5. DISGNOSING DIABETES MELLITUS

 Salient Features (MIMS)

 1. Symptoms include-                                                                                                                i. Polyuria and/or polydipsia                                                                                                  ii.Visual blurring                                                                                                                    iii.Balanitis                                                                                                                            iv. Candidiasis                                                                                                                      v.Recurrent skin infections                                                                                                    vi..Lethargy                                                                                                                          vii..Weight loss

2.Diagnosis can be based on a single, random venous plasma glucose reading of at            least 11.1mmol/ L (200mg/dL)       

3.Alternatively, diagnosis can be based on a single fasting, venous plasma glucose             reading of at least 7.0mmol/L (130mg/dL); the duration of the fast should be between       8 and 14 hours

B. Diagnosis in asymptomatic patients

1. Diagnosis must be based on two samples on different days, both of which must be in      the diabetic  range         

2. If these levels are not diagnostic, a 75g oral glucose tolerance test is indicated. The patient is diabetic if the glucose level is more than 11mmol/L at hours(200mg/dL)

C. Borderline results

1. Impaired fasting glycaemia is defined as a fasting plasma glucose of 6.0mmol/L (110-      130mg/dL). In the cases, an oral glucose tolerance test is indicated to exclude                  diabetes

2.Impaired glucose tolerance is defined  as fasting plasma glucose in the non-diabetic         range i.e.less than 7.0mmol/L (130mg/dL), but a 2 hour oral glucose tolerance test           value of 7.8mmol/L dL inclusive (140-200mg/dL)

3.Patients with impaired tolerance test are not at risk of microvascular events than               normoglycaemic patients  

D. Unreliable tests

1.Glycosuria and finger prick tests should not be relied on to make a diagnosis

2.Measurement of glycosylated haemoglobulin (HBA1c) is also not recommended for        diagnosing diabetes

FACTS ON FINGER TIPS

6. GRAVE’S DISEASE

  Salient Features (MIMS)

 Pathophysiology and epidemiology

  1.Grave’s disease is an autoimmune disorder in which antibodies are directed against         thyroid-  timulating hormone receptors                                                                            2. Most cases occur in females and the peak age of onset is at 30 to 60 years                  3.This condition may run in families   

Clinical Features

1.Presents with features of hypothyroidism                                                                           2. Euthyroidism or hypothyroidism may ensue                                                                     3. Eye signs: exophthalmos and ophthalmoplegia                                                               4. Skin and nail signs: swelling and discoloration around the lateral malleoli; clubbing of       fingers                                                                                                                           5. Neck: goitre and bruits over thyroid gland

Investigations

1.Thyroid function tests                                                                                                         2. An autoantibody screen                                                                                                   3. A thyroid ultrasound scan is performed to exclude other causes of hyperthyroidism

Management

1. Refer to endocrinologist and ophthalmologist if needed.                                                   2. Treat throtoxoicosis symptomatically and with carbimazole or polythiouracil   

Key points                                                                                                                                               

1. Eye symptoms may be an early manifestation.                                                                 2. They may persist even after normal thyroid status has been restored                             3. Neonatal hyperthyroidism may occur in infants born to mothers with Grave’s disease