Hypopituitarism in elderly � A case series

Hypopituitarism is found to be one of the under investigated disease in elderly as it produces non specific symptoms which can be easily attributed to ageing and related co morbidities. Unless the hypopituitarism is identified and proper therapy is instituted, the clinical consequences of the untreated patients will be fatal. Here we report three cases of hypopituitarism in elderly patients whose clinical presentation and etiology was completely different. The first patient was fifty year old lady who is a known asthmatic for the past thirty years on steroids and had iatrogenic Cushing抯. On tapering the steroids she developed hypotension and giddiness. On eliciting the history she was suspected to have Sheehan抯 syndrome and was confirmed with investigations. She was advised to continue the steroids with calcium supplements. The second patient is an 80 years old female who came with complaints of increased tiredness daily more in the morning while getting up and improves slowly in the afternoon time and getting tired again in the night. When she was examined she had hypotension of 90/50 mm of hg. She was evaluated for Partial hypopituitarism and investigation confirmed hypopituitarism and she was started on Hydrocortisone tablets and she improved. The third patient was a 65 year old lady who was diagnosed to have diabetes mellitus and hypothyroidism and was on oral hypoglycemic drugs and eltroxine supplementation respectively. She had multiple hypoglycemic symptoms unresolved in spite of tapering the oral hypoglycemic drugs and on evaluation found to have partial hypopituitarism and started on T. Hydrocortisone and she improved well. We report these three cases as hypopitiutarism has multifaceted clinical presentation and needs high level of suspicion to diagnose it in elderly

Disseminated histoplasmosis: A comparative study of the clinical features and outcome among immunocompromised and immunocompetent patients.

Background. Disseminated histoplasmosis is a chronic granulomatous disease caused by the dimorphic fungus, Histoplasma capsulatum. Clinical presentation can vary from the acute pulmonary to the chronic disseminated form. In India, disseminated histoplasmosis often presents with pyrexia of unknown origin with a presentation similar to ‘disseminated tuberculosis’ involving the adrenal glands and bone marrow. Due to rarity of the disease, data are lacking regarding its clinical presentation and outcome among immunocompromised and immunocompetent patients. Methods. During January 2000 to December 2010, we identified 37 patients of disseminated histoplasmosis and attempted to characterize the differences between immunocompromised and immunocompetent patients. Demographic characteristics, clinical presentation, risk factors, laboratory findings, diagnostic yield, treatment received and prognosis were noted and compared between the two groups. Results. Eleven of 37 patients with disseminated histoplasmosis were immunocompromised and 26 were immunocompetent. Comparison of their clinical features showed a higher frequency of skin lesions in the immunocompromised compared to the immunocompetent group (54.5% v. 11.5%). Pancytopenia and anaemia were more common among the immunocompromised (81.8%) compared to the immunocompetent (46.2%) group. In the immunocompromised patients, the diagnosis was made most often by bone marrow aspirate and culture (72.7%) compared to the immunocompromised group where the diagnosis was most often obtained by adrenal gland biopsy and fungal cultures (57.7%). The cure rate was significantly higher in the immunocompetent group (73% v. 45%). Conclusion. The clinical presentation and outcome of patients with disseminated histoplasmosis differs among immunocompromised and immunocompetent patients.

Hypertensive crisis in a patient with thyroid cancer.

Phaeochromocytomas may be discovered incidentally when patients present with hypertensive crisis during general anaesthesia. A 49-year-old man underwent thyroidectomy 25 years ago and was diagnosed to have spindle cell carcinoma of the thyroid. He presented with recent onset of hoarseness of voice and was found to have a vocal cord nodule. He developed a hypertensive crisis during surgery. He was subsequently evaluated and found to have bilateral phaeochromocytoma. Further evaluation revealed a RET proto-oncogene mutation at codon 634 consistent with multiple endocrine neoplasia (MEN)-2A.

25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity.

Background & objectives: Western studies show that up to 65 per cent of patients with Crohn’s disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn’s disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients. Methods: Adult patients with Crohn’s disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed. Results: Thirty four patients with Crohn’s disease (M:F, 24:10, age 39.2 ± 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 ± 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn’s disease as compared to controls (Crohn’s disease vs controls: 16.3 ± 10.8 vs 22.8 ± 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level. Interpretation & conclusions: Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn’s disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn’s disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.

Accuracy of filter paper method for measuring glycated hemoglobin.

BACKGROUND AND OBJECTIVES: Glycated hemoglobin (HbA1c) provides an accurate and reliable method to assess the glycemic control in patients with Diabetes. Its measurement is limited by the inconvenience of sample collection that requires venipuncture, sample handling and storage factors. The aim of this study was to assess the feasibility of using a dried capillary blood spot on a filter paper to estimate HbA1c, to check its stability at room temperature and to compare these values with the venous sample HbA1c by Turbidimetric Inhibition Immunoassay (TINA, Tina-quant HbA1c II). METHODS: Venous blood samples of seventy eight patients with Type 1 or type 2 diabetes, were collected in EDTA containing vacutainers. Stability of HbA1c was studied in capillary blood samples blotted on to Whatman number 1 filter paper and stored at room temperature, for the first 20 patients enrolled in the study. After establishing the stability over a ten day period, HbA1c values obtained on the capillary blood spots were compared with those obtained from the venous blood samples of the remaining 58 patients. RESULTS: Glycated hemoglobin is found to be stable in dried capillary blood spots on filter paper till the 10th day, stored at room temperature. It however, shows an inherent variability of +/- 15%, which falls within the permissible variability (18%) of the quality control material. Seventy nine percent of the capillary HbA1c values were found to fall within this range. With linear regression, we derived the relationship between filter paper and venous HbA1c values. The regression equation was as follows: Cap.HbA1c = 0.95 (Ven.HbA1c) + 1.4. The filter paper results were highly correlated with the venous sample values (r = 0.889, p < 0.01). CONCLUSION: Measurement of glycated hemoglobin in dried blood spots on filter paper gives reliable and reproducible results. In our study, the mean capillary sample HbA1c value was 12% higher compared to the venous sample HbA1c values. Therefore a higher normal range may have to be used for interpreting the dried blood spot capillary blood HbA1c values.

Paget's disease of bone: experience from a centre in southern India.

BACKGROUND: Paget's disease is a localized disorder of the skeleton characterized by increased osteoclastic activity. While the prevalence in the Western Population is 1-2%, the prevalence in India is not known. We studied the clinical profile, biochemical parameters, bone scans, therapeutic details and follow up data of patients with Paget's disease, attending the Endocrinology outpatient clinic in our institution. METHODS: A retrospective review was done of the medical records of 51 patients seen in a tertiary referral centre in Southern India from 1995 to 2003.The data was analyzed using SPSS 9.0 software package. RESULTS: There were a total of 51 patients (41 male and 10 female). The mean age at presentation was 56 years and the mean duration of symptoms was 43 months. At least 6 months of follow-up was available in 31 patients and longer term (>2 years) follow-up in 22 patients. The symptoms at presentation were bone pain in 65%, low backache in 37%, skeletal deformities in 33%, pathological fractures in 20%, neurogenic claudication in 4%, deafness and head enlargement in 7% and renal stones in 4% of subjects. Five patients (9.8%) were asymptomatic and were incidentally diagnosed during evaluation of an elevated alkaline phosphatase. The mean serum alkaline phosphatase (range and SD) at the time of presentation was 690 IU/L (91-3873 U/L, 698 U/L). There was no statistically significant difference in the serum alkaline phosphatase values between female and male patients (576 U/L versus 718 U/L). Polyostotic involvement was seen in 90.2% of the patients. The pattern of skeletal involvement was very similar to that described in the Western literature. Twenty patients were started on Calcitonin and of these, 13 patients were later changed over to bisphosphonates to induce remission. In all, thirty six subjects received Alendronate and of them, 31 received lower doses (10-20mg/day). All the treated patients showed a good clinical and biochemical improvement. Two patients with severe Pagetic involvement of the bone who also had neurologic symptoms (root pains in one and cauda equina lesion in the other) needed intravenous Pamidronate to obtain a rapid response in the initial phase of treatment. CONCLUSIONS: In our series, Paget's disease had a male predominance. The clinical presentation and the pattern of skeletal involvement was similar to the Western series. Serum alkaline phosphatase declined by 40% at 6 months of therapy and by 64% by one year of treatment in patients who were on lower doses of Alendronate (10-20 mg/day) in our series, which is similar to what has been described with conventional doses (40 mg per day) in the Western series.

Hemorrhagic necrosis of pituitary adenomas.

A clinicopathological study of 41 cases of pituitary apoplexy in a series of 324 surgically treated pituitary adenomas is presented. In 23 patients, the predominant operative finding was hemorrhage with or without necrosis. However, there were 15 (37.7%) cases where pale, necrotic tissue with no evidence of hemorrhage was found at surgery. Pale, necrotic material was particularly found when there was a long interval between the acute clinical event and surgery. It is concluded that the pale, necrotic debris represents one stage in the resorption process of blood after hemorrhagic necrosis of pituitary adenomas. This entity needs to be kept in mind especially since the material closely resemble the pultaceous material seen in craniopharyngiomas and epidermoid cysts.

The 'hook effect' on serum prolactin estimation in a patient with macroprolactinoma.

Large quantities of antigen in an immunoassay system impair antigen-antibody binding, resulting in low antigen determination. This is called the 'high dose hook effect'. We report this phenomenon in a patient with a large macroprolactinoma. In this patient, the correct estimate of serum prolactin (PRL) was obtained only after appropriate dilution of serum. We suggest that in order to avoid the high dose hook effect, the serum PRL be estimated in appropriate dilution in all patients with large pituitary tumours. This is particularly important when the clinical suspicion of high PRL is strong, as in women with amenorrhoea-galactorrhoea and men with long standing hypogonadism.

Aetiology and treatment response in patients with spontaneous diabetes insipidus.

BACKGROUND: Spontaneous diabetes insipidus (DI) is an uncommon disorder. This study analysed aetiology and response to treatment in patients with spontaneous DI admitted to the endocrinology service of a teaching hospital. METHODS: Twenty patients were seen over a eight year period (1991-1998). The diagnosis of DI was confirmed in each case by the standard water deprivation test. Appropriate diagnostic procedures were carried out to determine aetiology. RESULTS: Sixteen patients had complete DI and four patients had partial DI. Eighteen had central DI and two nephrogenic DI. The etiology in sixteen of the eighteen patients with central DI included: histiocytosis--three, eosinophilic granuloma--two, neurosarcoidosis--three, viper-bite--one, head injury--two, germinoma--one, post RT--one, tuberculous meningitis--one, acute-sphenoid sinusitis--one and hypothalamic tumour--one. Eleven patients (61%) responded to tab. carbamazepine, while nine (45%) required intra-nasal DDAVP. One of the two patients with nephrogenic DI responded to thiazide diuretic. CONCLUSION: We identified the aetiology in 88% of our patients with central DI. Histiocytosis and sarcoidosis accounted for 40%. Most patients (61%) responded to treatment with oral carbamazepine, others required intra-nasal DDAVP.

Conn's syndrome: a simple diagnostic approach.

BACKGROUND: Primary aldosteronism is usually diagnosed after a battery of biochemical tests and adrenal imaging. If an adrenal tumour (Conn's syndrome) is identified, patients need surgery. However, bilateral adrenal hyperplasia is treated medically. Till 1994, we diagnosed Conn's syndrome using simple biochemical tests and a CT scan of the adrenal glands. Aldosterone and plasma renin activity assay became available in our institution in 1994 and were used subsequently in the work up of patients suspected to have Conn's syndrome. We analysed our data to determine whether simple tests such as serum and urinary potassium values combined with CT imaging of the adrenal glands are adequate to arrive at a diagnosis in these patients. METHODS: All consecutive patients (n = 17) diagnosed to have Conn's syndrome, managed by the Departments of Endocrinology and Surgical Endocrinology of this institution during a nine-year period from 1990 to 1998, were studied retrospectively. RESULTS: Until 1994, Conn's syndrome was diagnosed after documenting hypertension, hypokalaemia, inappropriate kaliuresis, metabolic alkalosis and CT scanning to localize the tumour. Serum aldosterone and plasma renin activity (PRA) were used in addition since 1994. All patients underwent adrenalectomy after adequate preoperative preparation. There was no operative mortality. Postoperatively, normokalaemia was established in all patients. Persistent postoperative hypertension was present in 43.8% of patients. CONCLUSIONS: In our experience, Conn's syndrome could be diagnosed accurately with simple investigations and CT imaging of the adrenal glands. Extensive biochemical testing, including aldosterone and PRA assay, is helpful when the diagnosis is uncertain. While hypokalaemia is curable after surgery, residual hypertension persists in about 45% of patients.

Analysis Of Y-Linked Lineage Markers In Indian Populations.

Recently, Y-linked markers have been found extremely useful tools in population genetics and evolutionary biology. We have studied a tetranucleotide marker, DYS19 and a bialleleic marker DYS287, an Alu polymorphic marker (YAP) in five ethnic groups of India. Blood samples were collected from 215 random healthy males and DNA was extracted by using a simple salt precipitation method. DNA samples, after amplification by polymerase chain reaction (PCR), were electrophoresed. The detection of alleles was done by silver staining and reconfirmed by using a fragment analyser programme in an ALF express sequencer (Pharamacia). A total of four alleles were observed at DYS19 locus in all the five ethnic groups. Allele 194bp was found to be the predominant one in all the groups. The absence of YAP was found in all the groups.

D17S5 Minisatellite In Two Maharastrian Indian Populations : Overcoming The Differential Amplification At This Locus Using Expand Long Template PCR System.

The D17S5 is a highly informative minisatellite locus and shows extensive interpopulation allelic variability. However in many cases, it shows preferential amplification of shorter alleles, which has hampered the full potential of this minisatellite from being realized. This study explores the use of the Expand Long Template PCR system to circumvent this problem.

D1S80 Minisatellite - Polymorphism In Five Ethnic Populations Of Maharashtra And Kerala.

The minisatellite locus D1S80 was studied in five ethnic populations, namely, Konkanastha Brahmins and Marathas of Maharashtra; Nairs, Ezhavas and Muslims from Kerala, to compare the allele and genotype frequencies. DNA isoleted from blood samples collected from 364 unrelated healthy donors was amplified by PCR and subjected to polyaerylamide gel electrophones. A total of 20 alleles and 71 genotypes were observed from the above population groups. A bimodal pattern was observed in the allele frequency distribution representing 18 and 24 as predominant ones. The observed heterozygosity was in the range of 65% to 82%. All the five population groups conformed to Hardy- Weinberg equilibrium expectations.

Studies On ApoB VNTR In Two Maharashtrian Ethnic population Groups.

The ApoB VNTR locus was analyzed in two distinct ethnic groups of Maharashtra to determine, the distribution of allele and genotype frequencies. Blood samples were collected from 183 random, unrelated, healthy donors. DNA was extracted by using a simple salt precipitation method, amplified by polymerase chain reaction (PCR) and the products were electrophoresed in 4% PAGE followed by silver staining. A total of 14 alleles and 38 genotypes were observed. Allele 37 and 39 were found to be the predominant alleles showing a bimodal distribution. Both the population groups conformed to Hardy-Weinberg Equilibrium expectations.