Osteoporosis in Parkinson's Disease: Relevance of Distal Radius Dual-Energy X-Ray Absorptiometry (DXA) and Sarcopenia.

Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [ORadjusted] = 11.3, 95% confidence interval [CI]: 2.6-48.6) and sarcopenia (ORadjusted = 8.4, 95% CI: 1.1-64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research.

A Case of Severe Lactation Ketoacidosis in a Nondiabetic Mother on a Ketogenic Diet.

Lactation ketoacidosis is a rare yet severe metabolic emergency that has been reported in breastfeeding mothers. Reduced carbohydrate intake during breastfeeding has been reported as a common trigger for ketoacidosis. We report the case of a 31-year-old mother without diabetes who presented with life-threatening lactation ketoacidosis after following a ketogenic diet while exclusively breastfeeding her newborn baby. She was managed in the intensive care unit with dextrose and insulin infusion to reverse ketoacidosis. With prompt treatment, the patient's ketoacidosis resolved within 24 hours, and she was discharged well 3 days later. We further discuss the underlying increased metabolic demand in lactating women that puts them at risk of ketoacidosis, underlining the importance of early recognition of lactation ketoacidosis and nutritional education for lactating women.

A summary of the Malaysian Clinical Practice Guidelines on the management of postmenopausal osteoporosis, 2022.

Objectives: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP). Methods: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation. Results: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients' fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate. Conclusions: The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.

Relationship of glycated hemoglobin, and fasting and postprandial hyperglycemia in type 2 diabetes mellitus patients in Malaysia.

AIMS/INTRODUCTION: Studies on the relative contributions of fasting and postprandial hyperglycemia (FH and PPH) to glycated hemoglobin (HbA1c ) in patients with type 2 diabetes have yielded inconsistent results. We aimed to assess the relationship by using continuous glucose monitoring in a multi-ethnic cohort. MATERIALS AND METHODS: A total of 100 adults with type 2 diabetes were assessed with 6-day continuous glucose monitoring and HbA1c . Area under the curve (AUC) ≥5.6 mmol/L was defined as AUCTOTAL . AUC equal to or greater than each preprandial glucose for 4-h duration was defined as AUCPPH . The total PPH (AUCTPPH ) was the sum of the various AUCPPH. The postprandial contribution to overall hyperglycemia was calculated as (AUCTPPH / AUCTOTAL ) × 100%. RESULTS: The present study comprised of Malay, Indian, and Chinese type 2 diabetes patients at 34, 34 and 28% respectively. Overall, the mean PPH significantly decreased as HbA1c advanced (mixed model repeated measures adjusted, beta-estimate = -3.0, P = 0.009). Age (P = 0.010) and hypoglycemia (P = 0.006) predicted the contribution difference. In oral antidiabetic drug-treated patients (n = 58), FH contribution increased from 54% (HbA1c 6-6.9%) to 67% (HbA1c ≥10%). FH predominance was significant in poorly-controlled groups (P = 0.028 at HbA1c 9-9.9%; P = 0.015 at HbA1c ≥10%). Among insulin users (n = 42), FH predominated when HbA1c was ≥10% before adjustment for hypoglycemia (P = 0.047), whereas PPH was numerically greater when HbA1c was <8%. CONCLUSIONS: FH and PPH contributions were equal in well-controlled Malaysian type 2 diabetes patients in real-world practice. FH predominated when HbA1c was ≥9 and ≥10% in oral antidiabetic drug- and insulin-treated patients, respectively. A unique observation was the greater PPH contribution when HbA1c was <8% despite the use of basal and mealtime insulin in this multi-ethnic cohort, which required further validation.

Maintenance vitamin D3 dosage requirements in Chinese women with post menopausal osteoporosis living in the tropics.

BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics. METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks. RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity. CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.

PRKAR1A-negative familial Cushing's syndrome: two case reports.

INTRODUCTION: Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood. CASE PRESENTATION: A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level <5 pg/ml). Computed tomography of her adrenal glands revealed a 0.7-cm left adrenal hypodense nodule. After a left adrenalectomy, she had residual hypercortisolism (progressive weight gain, new T10 compression fracture, and not glucocorticoid-dependent postoperatively). Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen. Similarly, her younger brother developed adrenocorticotropic hormone-independent Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex. CONCLUSIONS: The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have bilateral/multiple adrenal nodules or normal adrenal glands visualized by computed tomography. Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.