Frequency of Macroprolactin in Hyperprolactinemia.

OBJECTIVE: To determine the frequency of Macroprolactin (MaPRL) in patients with increased total prolactin and its clinical and financial impact. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from March to May 2015. METHODOLOGY: Patients with high total prolactin were screened by polyethylene glycol (PEG) precipitation for determination of MaPRL. Clinical history, imaging work-ups, and cost incurred in further investigations were collected by telephonic interview after verbal consent. Patients were stratified into true hyperprolactinemia and macroprolactinemia after PEG treatment, based on monomeric prolactin levels. Medical records of cases registered with AKUH were reviewed to confirm the diagnosis. RESULTS: Two hundred and thirty-nine patients were identified with high prolactin levels. Macroprolactinemia was identified in 145 (60.7%) and true hyperprolactinemia in 94 (39.3%) patients. Galactorrhea was significantly more in true hyperprolactinemic females (p=0.022), followed by visual disturbances (p=0.01) and headache (p=0.006). Moreover, as majority of population were females, the clinical features in the macroprolactinemia group as compared to true hyperprolactinemic group were mostly related to non-pituitary causes like drug intake [42.5% (54) vs. 37% (30)], heat intolerance due to thyroidal illness [41.7% (53) vs. 38.3% (31)] and surgery [26.8% (34) vs 22.2% (18)] in females. Further radiological workup (MRI, CT) were conducted in 35 (37.2%) patients with true hyperprolactinemia. Twenty-one (60%) of the patients were confirmed to have pituitary adenomas. In eight (5.5%) patients with MaPRL, only one had pituitary microadenoma on radiological workup. Total cost impact on the basis of investigations, was significantly higher in the group undergone imaging, despite 7 out of 8 individuals found to have normal imaging results. The median total cost in true hyperprolactinemic group undergone imaging was Rs. 4370 (IQR=2412.5, 22850) as compared to macroprolactinemic groups; Rs. 3,250 (IQR=2150, 4278). There was significant difference in the cost burden of both the groups (p <0.001). CONCLUSION: High frequency of MaPRL was identified in patients with hyperprolactinemia. Screening with PEG precipitation in hyperprolactinemic sera is simple and cost-effective.

Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani Children.

OBJECTIVE: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years. STUDY DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014. METHODOLOGY: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician. RESULTS: Eighty-eight cases (4.7%) were diagnosed including 41 OA (46.5%), 28 AA (31.8%) and 19 others (21.5%) from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate (64.8%). Among OA, methyl CoA mutase deficiency was diagnosed in 9 (10.2%) and was suspected in 2 (2.3%) cases. Five (5.7%) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5%) each of PPA (propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4%) cases each of IVA (isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1) and 2 (2.3%) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1%) cases of MSUD (maple syrup urine disease), 6 (6.8%) cases of CBS (cystathionine beta-synthetase) and UCDs (urea cycle disorders) each, 5 (5.7%) cases of hyperphenylalaninemia and 3 (3.4%) cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 (10.2%) cases of intracellular cobalamin defects, 2 (2.3%) cases each of alkaptonuria, Canavan's disease, SUCL (succinate CoA ligase) deficiency, and 1 (1.1%) case each of DPD (dihydropyrimidine) deficiency, GA-2, NKH (non-ketotic hyperglycinemia), AADC (aromatic amino acid decarboxylase) deficiency. CONCLUSION: This study presents frequency of OA and AA in the high-risk Pakistani pediatric population analyzed locally.