Testing Endocrine Function

Prolactin - check prolactin level.

Growth hormone

• Basal growth hormone level does not determine GH deficiency because 50% of a person's GH levels are undetectable in a 24-hour period. At the same time there are pulses of growth hormone secretion which are almost impossible to distinguish from acromegaly.

• Basal IGF - 1 level - useful for deficiency as well as excess of growth hormone secretion. Some clinicians advocate that stimulation testing may not be required in patients with other anterior pituitary hormone deficiencies and a low IGF-1 level.

• Insulin tolerance test - the gold standard test for the diagnosis of GH deficiency.

• GH-releasing hormone-arginine test is as accurate as ITT and it is less dangerous.

• Oral glucose tolerance test showing an elevated IGF-1 value and an elevated GH value with failure to suppress after oral glucose administration is suggestive of acromegaly.

Hypothalmo-pituitary-adrenal axis

Mineralocorticoid deficiency

• Undetectable serum cortisol is diagnostic of adrenal insufficiency. A cortisol > 580 nmol/L precludes the diagnosis of adrenal insufficiency.

• Short synacthen test can be used to confirm the adrenal insufficiency.

Mineralocorticoid excess

• Aldosterone renin ratio is the best screening test for hyperaldosteronism. The ratio is unaffected by most antihypertensive except spironolactone.

• 24 hr urinary aldosterone collection can be confirmatory for hyperaldosteronism.

• Intravenous saline loading test to assess suppression of aldosteronecan also be used to confirm the diagnosis.

Chronic Myeloid Leukaemia

50 % of patients are asymptomatic but splenomegaly present in > 50 % of cases of CML in the initial chronic phase.

• Diagnosis is based on blood counts and proof of diagnosis is attained by demonstration of philadelphia chromosome, t ( 9;22 ).

The typical clinical course is triphasic:

• Chronic phase

• Accelerated phase ( 15 - 29 % of blast in blood or BM, more than 20 % basophils in blood, thrombocytosis or thrombocytopenia unrelated to therapy or clonal cytogenetic evolution.
  

• Blast phase/ blast crisis ( 30 % or more of the blasts in blood and bone marrow ).

The current standard therapy is Imatinib.

BRCA in breast cancer

Family susceptibility to breast cancer accounts for approximately 25 % of all breast cancer cases. However, in familial cancer, mutations in the BRCA 1/2, CHEK 2, TP53 and PTEN genes account for 5 -10 % of breast and ovarian cancer.

In unselected cases, BRCA 1 and BRCA 2 accounts for only 3 - 5 % of breast and ovarian cancer but higher prevalence is noted in those with a family history which are going to discuss later.

Women with BRCA 1 carries a life time risk of 80 % of developing breast cancer and 60 % of ovarian cancer, and with BRCA 2 have a life time risk of 80 % for breast cancer and 20 % for ovarian cancer.

Genetic testing criteria may differ between countries but widely accepted criteria for referral includes:

• three or more cases of breast cancer and / or ovarian cancer cases, at least one being diagnosed less than 50 years

• two breast cancer cases aged less than 40 years old

• male breast cancer

• bilateral breast cancer

Management:

Surveillance - self examinations and clinical examination twice a year together with yearly mammogram / MRI starting from age 25 - 30 years.

Chemoprevention - adjuvant tamoxifen reduces the risk of contralateral breast cancer in affected BRCA mutation carriers, while the benefit of tamoxifen for primary prevention has not been demonstrated.

Prophylactic bilateral mastectomy - most women find this strategy unacceptable for primary prevention. Contralateral prophylactic mastectomy is an option to consider in those carrier with early breast cancer.

Prophylactic bilateral salpingo-oophorectomy - it is associated with a risk reduction of breast cancer in premenopausal BRCA mutation carriers and risk reduction of ovarian cancer. It is recommended after age 35 and when child bearing decisons are complete.

Fertility Preservation in Cancer Patients

Gonadal toxicity can be resulted from ionising radiation and chemotherapeutic agents especially alkylating agents such as chlorambucil, cyclophosphamide and melphalan.

All patients at risk for infertility who have not completed childbearing should discuss germ cell storage options with the medical team.

Male - Semen cryopreservation of at least three samples with 48-h abstinence intervals is recommended. For azoospermic men, testicular sperm extraction may be an option for fertility preservation. Prepubertal males may participate in clinical research of testicular tissue/spermatogonial stem cell storage.

Female - Embryo cryopreservation and ovary transposition are the only established fertility preservation options for female patients. Experimental fertility preservation options are oocyte cryopreservation for women without a partner and ovarian tissue storage for those who cannot undergo ovarian stimulation or are prepubertal.

Opportunistic Infections

Toxoplasma gondii infection

• Disease occurs almost exclusively because of reactivation of latent tissue cysts. Primary infection occurs after eating undercooked meat containing tissue cysts or ingestion of oocysts that have been shed in cat feces.

• Clinical disease is rare among patients with CD4+ T lymphocyte counts >200 cells/μL. The greatest risk is among patients with a CD4+ T lymphocyte count less than 50.
  

• The most common clinical presentation of T. gondii infection among patients with AIDS is of a focal encephalitis.

• Patients with TE are almost uniformly seropositive for anti-toxoplasma IgG antibodies. The absence of IgG antibody makes a diagnosis of toxoplasmosis unlikely but not impossible. Anti-toxoplasma IgM antibodies are usually absent.

• CT/MRI scan can demonstrate mass lesion.

• CT guided brain biopsy can demonstrate Toxoplasma Gondi. Detection of T. gondii by PCR in cerebrospinal fluid has produced disappointing results.
  

• Differentials includes CNS lymphoma, mycobacterial infection (especially TB), fungal infection (e.g. cryptococcosis), Chagas disease, bacterial abscess, and rarely PML, which can be distinguished on the basis of imaging studies (PML lesions typically involve white matter rather than gray matter, are noncontrast enhancing, and indicate no mass effect).

• The initial therapy of choice consists of the combination of pyrimethamine plus sulfadiazine plus leucovorin. Acute therapy should be continued for at least 6 weeks, if there is clinical and radiologic improvement. Longer courses might be appropriate if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

Cryptosporidiosis

• Those at greatest risk for disease are patients with advanced immunosuppression (i.e., CD4+ T lymphocyte counts generally less than 100.
  

• Feces from infected animals, including humans, can contaminate water supplies and recreational water with viable oocysts despite standard chlorination.

• The most common presentation of cryptosporidiosis is the acute or subacute onset of profuse, nonbloody watery diarrhea. Cholangitis and pancreatitis occur among patients with prolonged disease.

• Diagnosis of cryptosporidiosis is primarily based on microscopic identification of the oocysts in stool or tissue. Cryptosporidial enteritis can be diagnosed on small intestinal biopsy.

• ART with immune restoration is associated with complete resolution and all patient should be offered ART. Chemotherapeutic and Immunotherapeutic agent does not have consistent success.

Microsporidiosis

• They are ubiquitous organisms and are likely zoonotic and/or waterborne in origin.

• The most common manifestation of microsporidiosis is diarrhea but encephalitis, ocular infection, sinusitis, myositis, and disseminated infection are also described.

• In gastrointestinal disease, examination of three stools with chromotrope and chemofluorescent stains is often sufficient for diagnosis. If stool examination is negative and microsporidiosis is suspected, a small bowel biopsy should be performed.

• ART with immune restoration is associated with complete resolution and all patient should be offered ART. Albendazole is also recommended for initial therapy.

Progressive Multifocal Leukoencephalopathy Caused by JC Virus

• PML is the only known disease caused by the JC virus. This disease has an insidious onset and characterized by cognitive dysfunction, dementia, seizures, ataxia, aphasia, cranial nerve deficits, hemiparesis or quadriparesis, and eventually coma.

• Typical computed tomographic abnormalities include single or multiple hypodense, nonenhancing cerebral white matter lesions, although cerebellum and brain stem are occasionally involved.

• Brain biopsy can demonstrate characteristic pathologic foci of demyelination and oligodendrocytes with enlarged nuclei and basophilic-staining intranuclear material. PCR detection of JC virus DNA in CSF provides supportive diagnostic information.

• No effective therapy for JC virus exists.

Adrenal Incidentaloma

During the evaluation of adrenal incidentaloma, two questions need to be asked:
1) is the the lesion hormonally active?
2) does it have radiologic characteristics suggestive of a malignant lesion?

Is the lesion hormonally active?

• The patient should be tested for hypercortisolism, hyperaldosteronism ( if hypertensive ) and phaeochromocytoma.

• Hypercortisolism - the simplest screening test is a 1 mg overnight dexamethasone suppression test. If clinical suspicion is high, such as in patients with hypertension, obesity, diabetes mellitus or osteoporosis, 3 tests ( salivary cortisol, dexamethasone suppression test and 24 hr urinary free cortisol ) can be used.

• Phaeochromocytoma - should undergo measurement of plasma fractionated metanephrines and normetanephrines or 24 hr total urinary metanephrines and fractionated catecholamines.

• Aldosteronism - an aldosterone-to-renin ratio should be performed and if > 20, further confimation by demonstrating lack of aldosterone suppression with salt loading.

Does it have radiologic characteristics suggestive of a malignant lesion?

• Although size should not be used as the only parameter to guide treatment, a 4-cm cutoff had a 93 percent sensitivity of detecting adrenocortical carcinoma, even though specificity was limited (76 percent of masses larger than 4 cm in diameter were benign). As a result, surgical removal of masses larger than 4 cm, particularly in younger patients is recommended.

• A homogeneous adrenal mass <4>50 percent at 10 minutes) is very likely to be a benign cortical adenoma.

• The imaging characteristics that suggest adrenal carcinoma or metastases include: irregular shape, inhomogeneous density, high unenhanced CT attenuation values (>20 HU), delayed contrast medium washout (eg, <50>4 cm, and tumor calcification.

Thryroid Nodule

Thyroid nodules are very common clinical finding with an estimated prevalence of 3 - 7 %.

Investigation:

Laboratory Evaluation

• Measurement of TSH concentration is the single most useful laboratory test in the initial evaluation of thyroid nodules.

• Thyroid peroxidase antibody should be measured in patient with high TSH level. Patients with raised TPO Ab and a firm, diffusely enlarged thyroid are very suggestive of autoimmune or Hashimoto's thyroiditis.

• Calcitonin level should be measured as it is a useful marker of medullary thyroid carcinoma, especially in patient with family history of MTC or MEN 2.

Diagnostic Imaging Studies

• High resolution USS is the most sensitive test available to detect thyroid lesions. Nodules with malignant potential should be identified and FNA biopsy should be suggested to the patients.

• Thyroid Scintigraphy is useful in hyperthyroid patient to differentiate cold and hot nodule.

Cytological Studies

• Fine needle aspiration cytology/ biopsy has been established as a safe and reliable. FNAC/B results can be

Diagonostic ( satisfactory specimen )

• Benign
• Malignant
• Suspicious

Non-diagnostic ( unsatisfactory speciment )

• Foam cells
• Cyst fluid
• Blood

Interpretation

Hyperthyroidism ( Low TSH ) - need scintigraphy

• Hot nodule - can be MNG or solitary thyroid nodule. MNG need further USS study to exclude for suspicious lesion and if required FNAC/B.

• Cold nodule - need further work up with FNAC/B.

Euthyroid - need further work up depending on the size and risk factors for malignant lesions.

• Risk factors includes:

History of head and neck irradiation
Family history of MTC or MEN 2
Age less than 20 or more than 70
Male sex
Growing nodule
Firm or hard consistency
Fixed nodule
Cervical adenopathy
Persistent hoarseness, dysphonia, dysphagia or dyspnoea

• More than 10 mm or risk factors - need FNAC/B.

• Less than 10 mm and no risk factors - USS first to look for suspicious lesion and if suggestive, FNAC/B.

Hypothroidism ( high TSH ) - need USS scan.

• If suspicious for malignancy on USS - then FNAC/B is warranted.

• If not suscpicious - then TPO Ab is suggested to confirm for Hashimoto's thyroiditis and autoimmune thyroiditis.

Hypogonadism

When hypogonadism develops before the age of puberty, the manifestations are those of impaired puberty:

• Small testes, phallus, and prostate
• Scant pubic and axillary hair
• Disproportionately long arms and legs (from delayed
• epiphyseal closure)
• Reduced male musculature
• Gynecomastia
• Persistently high-pitched voice

Postpubertal loss of testicular function results in slowly evolving subtle clinical symptoms and signs. In aging men, these symptoms and signs may be difficult to appreciate because they are often attributed to “getting older.” The growth of body hair usually slows, but the voice and the size of the phallus usually remain unchanged. Prostate size may decrease in hypogonadal men, but the amount of change is related to the severity of testosterone deficiency. Typical temporal hair recession and balding usually do not occur, and if they did, these manifestations would not be expected to prompt a patient to seek medical attention. Patients with hypogonadism may have the following findings:

• Progressive decrease in muscle mass
• Loss of libido
• Impotence
• Oligospermia or azoospermia
• Occasionally, menopausal-type hot flushes (with acute onset of hypogonadism)
• Poor ability to concentrate

The major objectives of the initial assessment of a patient with possible hypogonadism are to distinguish primary gonadal failure (hypergonadotropic hypogonadism with low testosterone and increased FSH and LH levels) from hypothalamic-pituitary disorders (hypogonadotropic hypogonadism with low testosterone and low to normal FSH and LH levels) and to make a specific diagnosis.

• Men with hypogonadotropic disorders may achieve fertility with gonadal stimulation.

• Men with hypergonadotropic disorders are treated with testosterone to achieve virilization and are usually, but not invariably, incapable of achieving fertility.

Investigation:

• Level of testosterone determination is the threshold test in the evaluation of suspected male hypogonadism.

• If the clinical findings indicate that hypogonadism is present and the total testosterone levels are normal or borderline low, the level of SHBG or free testosterone should be determined.

• Gonadotrophins ( FSH and LH ) is used to determine whether the hypogonadism is related to a primary testicular disorder or to pituitary disease. FSH has a longer half-life than does LH and is more likely to provide adequate results on a single blood sample.

• GnRH Stimulation Test

• In men with acquired hypogonadotropic hypogonadism, who usually have a reduced libido and impotence, a prolactin level should be determined to evaluate for the presence of a prolactinoma or other cause of hyperprolactinemia. High prolactin levels can reduce GnRH and testosterone levels.

• Pituitary Imaging

• Bone Mineral densitometry

Acromegaly

Acromegaly is often a chronic debilitating condition that, if left uncontrolled, is associated with increased morbidity and mortality.

GH stimulates hepatic production of insulin-like growth factor-I (IGF-I). GH produces some of its somatic effects directly; others are mediated by IGF-I.

Investigation:

Once acromegaly is suspected, measurement of serum IGF-I should be the next step. Acromegaly in the absence of high IGF-I levels is extremely rare.

Measuring GH during an OGTT has been a standard technique for diagnosis of acromegaly for almost 40 years. If the GH level does not decline to below 1 ng/mL during the test, the patient has acromegaly.

Although random GH levels are not generally useful in diagnosing acromegaly, patients with diabetes mellitus have
GH levels that respond to glucose; however, performance of an OGTT in patients with very high levels of glucose is not always advisable.

Low, but nonsuppressible, levels of GH after oral administration of glucose (GH >1 ng/mL) are frequently noted in patients who have undergone surgical treatment and who have normal IGF-I concentrations. In such patients, the acromegaly is considered controlled but not cured. If the patient is asymptomatic, close follow-up without therapy is reasonable. Currently, prophylactic irradiation is not considered warranted in this context. If symptoms such as heat intolerance or glucose intolerance emerge, or if the IGF-I level becomes high, further therapy is warranted.

Management:

Measurement of GHRH can be helpful in detecting an ectopic source of the acromegaly. A GHRH test should be done when a patient has no obvious pituitary tumor, but there is proven acromegaly.

• Surgical treatment should be considered the first therapeutic option in every patient with acromegaly. Those patients who present with severe mass effect manifested as visual loss or double vision are appropriate candidates for urgent surgical treatment.

• Medical therapy may be offered as first-line treatment but only after the surgical option has been discussed with the patient.

1. Somatostatin analogue such as octreotide.
2. GH receptor antagonists such as pegvisomant.
3. Dopamine agonist such as carbargoline.

• Pituitary irradiation is most commonly used as adjunctive therapy after surgical resection. In young adults who desire fertility, the patients (men and women) must be informed that any type of pituitary irradiation may impair gonadotropin function.

• Treatment of associated condition such as cardiovascular or respiratory condition. Colonoscopy should be done at the time of diagnosis of acromegaly and then follow guidelines (colonoscopy every 5 years if no cancer or polyps are detected, with more frequent follow-up if any lesions are detected ).

Heparin Induced Thrombocytopenia

Heparin may be used for both prevention and the treatment of thrombosis. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding.

Usual scenario:
Relative fall in platelet count >/50 % with absolute count of not less than 20 associated with

• arterial or venous thrombosis
• skin necrosis
• anaphylatoid reaction

There is no alternative explanation for thrombocytopenia.

A clinical probability score ( 4 Ts ):


Management:


Bilateral lower extremity compression USS should be performed in all patients with HIT, whether or not there is clinical evidence of lower limb DVT as it will influence the duration of anticoagulation.

For patients with HIT associated thrombosis, anticoagulate for a defined course typically 3 - 6 months as with other provoked thromboses.

For patients with HIT without thrombosis, the optimal duration of anticoagulation is unknown but anticoagulation for at least 0ne months is usual.

Non-heparin anticoagulants such as danaparoid, lepirudin and Fondaparinux is recommended.

HIT patients are at risk of venous limb gangrene during initiation of warfarin and warfarin should not be introduced until the platelet count is more than 150.

Renal Artery Stenosis

Renovascular hypertension is the systemic hypertension due to narrowing of the renal arteries. From a haemodynaemic point of view, a proximal stenosis is significant when there is a pressure gradient across the stenosis.

RAS has two main aetiologies: atherosclerosis and fibromuscular dysplasia.

Caring for Australasians with Renovascular Diesease ( CARI ) guidelines, the following classification has been devised based ont he likelihood of progression:

• Less than 50 % stenosis - insignificant
• 50 - 70 % stenosis - moderate
• more than 70 % stenosis - severe

Indication for screening RAS:

• Refractory hypertension ( > 160/100 mmHg and resistant to more than 4 antihypertensives )
• A greater than 40 % rise in serum creatinine level after the commencement of ACE inhibitor / ARB therapy.
• Progressive and rapid decline in renal function with other causes excluded.
• Proven episodes of pulmonary oedema and normal baseline left ventricular function.

Which Imaging tools to be used?

• Duplex ultrasonography - least invasive but subsequent tests are required due to high rate of false positive and negative results.
• Intra-arterial digital substraction angiography - definitive tool to diagnose the presence RAS.
• CT angiography - it is an accurate, minimally invasive screening test especially suited to the diagnosis of RAS due to fibromuscular dysplasia.
• Gadolinium enhanced MR angiography - highly sensitive in detecting atherosclerotic RAS and has significantly higher accuracy than any other modality in excluding the disease. However, the use of gadolinium is contraindicated in patients with GFR less than 30ml/min due to risk of nephrogenic systemic sclerosis.

Management:

Medical Therapy - In unilateral RAS, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are useful for their ability to improve blood pressure and their overall cardiovascular benefit. a small initial rise in serum creatinine ( less than 30 % ) is transient and acceptable.

In bilateral RAS, ARB and ACEI are considered contraindicated. Acute renal failure occurs in about 30 % of patients but is usually reversible. In some patients, ACEI/ARB has high benefits, such as congestive cardiac failure patient, ACEI and ARB should be initiated in hospital setting.

Endovascular Treatment - There has been no difference in either blood pressure reduction and renal decline after 12 months when medical therapy has been compared with endovascular therapy.
Disappointly, the adverse event rate in those undergoing angioplasty has ranged from 10 - 25 %.

It seems reasonable to restrict renovascularisation to those patients with high grade stenosis ( > 70 % ) and with specific clinical problems:

• Refractory hypertension ( > 160 mmHg ) and resistant to more than four antihypertensive agents
• > 30 % rise in creatinine level on commencement of ACEI
• Progressive vascular renal decline
• Recurrent, unexplained pulmonary oedema with normal left ventricular function on echocardiography

Post Transplant Lymphoproliferative Disorder ( PTLD )

In the first year after organ transplantation, recipients are at the greatest risk of developing lymphoproliferative diseases (PTLDs), which are induced most often by Epstein-Barr virus (EBV) infection, and patients should therefore be screened prior to or at the time of transplantation for EBV antibodies.

In the rare cases (<5%) where the recipient is EBV seronegative, he or she has a 95% likelihood of receiving an organ from an EBV-seropositive donor, which translates into a high risk of primary EBV infection with seroconversion soon after transplantation. In such cases, the recipient should receive a prophylactic antiviral treatment with acyclovir, valacyclovir or ganciclovir, starting at the time of transplant and lasting for at least 3 months.

The treatment of PTLD should be based on accurate pathology with extensive cell markers and phenotyping.

The treatment modalities are as follows.

• Reduction of basal immunosuppression in all cases (either maintain only steroids, or decrease by at least 50% the anti-calcineurin drugs and stop other immunosuppressive drugs).

• In the case of EBV-positive B-cell lymphoma, antiviral treatment with acyclovir, valacyclovir or ganciclovir may be initiated for at least 1 month or according to the blood level of EBV replication when available.

• In the case of rare lymphomas from the mucosal-associated lymphoid tissue (MALT) with positive Helicobacter pylori, full eradication of H. pylori should be carried out. Subsequent H. pylori prophylaxis should be implemented to avoid relapse.

• In the case of CD20-positive lymphomas, treatment with rituximab, a chimeric monoclonal antibody directed against CD20, should be carried out with one i.v. injection per week for 4 weeks.

• In the case of diffuse lymphomas or improper response to previous treatment, CHOP chemotherapy should be used alone or in combination with rituximab. The CHOP regimen is cyclophosphamide, doxorubicine, vincristine and prednisone.

• Complete cessation of immunosuppression with or without graft nephrectomy should also be considered.

PCP prophylaxis post renal transplant

Approximately 5% of patients develop Pneumocystis carinii pneumonia (PCP) after renal transplantation if they do not receive prophylaxis.

PCP is a severe disease, with a very high fatality rate. Therefore, all renal transplant recipients should receive PCP prophylaxis.

The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of 80/400 mg/day or 160/800 mg every other day, for at least 4 months.

Patients who are treated for rejection should receive TMP-SMX prophylaxis for 3-4 months.

In the case of TMP-SMX intolerance, aerosolized pentamidine (300 mg once or twice per month) is an alternative for prophylaxis.

The first-line treatment of PCP is high-dose TMP-SMX. Patients with a PaO2 of <70 mmHg initially should be treated parenterally, and the administration of additional steroids should be considered.

Pregnancy and Transplantion

Women with end stage kidney disease have hypothalmic gonadal dysfunction and infertility. Infertility also occurs with end-stage disease of other organs such as heart, liver and lung.

However, there is still a risk of unwanted pregnancy and so all women with end-stage organ disease who are of child bearing age need effective contraception.

Within the first months after transplantation, gondal dysfunction rapidly reverses, and female fertility returns, conferring a substantial possibility of conception.

Most transplantation centres have advised that conception is safe after the second post-transplantation year, on the assumption that the graft function well. A consensus conference held by the Women's Health Committee of American Society of Transplantation in 2003 concluded that pregnancy is usually safe after the first year, provided that allograft function is stable and that no rejection episodes have occurred in the year before conception.

Pregnancy after transplantation should be considered a high-risk pregnancy and should be monitored by both an obstetrician and the transplant physician.

Pregnancy should be diagnosed as early as possible.

The principal risks are infection, proteinuria, anaemia, arterial hypertension and acute rejection for the mother, and prematurity and low birth weight for the foetus.

Pregnant women and transplanted patients are at increased risk of infections, especially bacterial urinary tract infections and acute pyelonephritis of the graft.

Urine cultures should be performed monthly and all asymptomatic infections should be treated. Monitoring of viral infections is also recommended.

Acute rejection episodes are uncommon but may occur after delivery. Therefore, immunosuppression should be re-adjusted immediately after delivery.

Because pre-eclampsia develops in 30% of pregnant patients, especially those with prior arterial transplant hypertension, blood pressure, renal function, proteinuria and weight should be monitored every 2-4 weeks, with more attention during the third trimester. Anti-hypertensive agents should be changed to those tolerated during pregnancy. ACE inhibitors and angiotensin II receptor antagonists are absolutely contra-indicated.

Immunosuppressive therapy based on cyclosporine or tacrolimus with or without steroids and azathioprine may be continued in renal transplant women during pregnancy. Other drugs, such as mycophenolate mofetil and sirolimus, are not recommended.

Vaginal delivery is recommended, but caesarean section is required in at least 50% of cases. Delivery should occur in a specialized centre.

In the puerperium, renal function, proteinuria, blood pressure, cyclosporine/tacrolimus blood levels and fluid balance should be closely monitored.

Because of drug transfer into maternal milk, breastfeeding is not recommended.

Differential Diagnosis of chronic Renal Graft Dysfunction

Any significant deterioration in graft function should be investigated using the appropriate diagnostic tools and, if possible, therapeutic interventions should be initiated. The usual causes of a decline in glomerular filtration rate after the first year include:

Causes related to allograft includes:

• Chronic allograft rejection
• Acute rejection
• Transplant renal artery stenosis
• Ureteric obstruction
• Recurrent and De novo glomerlonephritis
• BK virus nephropathy
• Calcineurin induced nephropathy
  

Causes not related to allograft includes:

• Pre-renal
• Renal
• Post-renal