OBJECTIVES

Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.

METHODS

This was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.

RESULTS

Two hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.

CONCLUSION

Overall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.

Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce

Introduction: Medullary thyroid carcinoma (MTC) comprises sporadic and hereditary forms, the latter commonly associated with multiple endocrine neoplasia type 2 (MEN2) which is identifiable through genetic screening of germline RET protooncogene. We compared the clinicopathological features and outcomes of hereditary and sporadic MTC in our single centre. Methodology: We conducted a retrospective audit of patients with MTC from 2000 to 2026. Patients were classified as either hereditary or sporadic based on genetic testing and/or family history of MTC/MEN2A syndrome. Variables analyzed included age at diagnosis, mode of presentation, pre-operative calcitonin, tumor size, lymph node (LN) involvement, post-operative biochemical cure, repeat surgery and presence of structural residual/recurrent disease. Results: A total of 57 patients were included (18 hereditary [31.6%], 39 presumed sporadic [68.4%]) with a median follow-up of 7.5 years (IQR 1.5–12.4). Hereditary MTC was diagnosed at a significantly younger age than sporadic MTC (33.0 vs. 44.7 years, p = 0.010) where 33% of the cases were diagnosed via screening detection whereas sporadic MTC more commonly presented with symptomatic neck swelling (84.6% vs. 50.0%, p = 0.008). There were no significant differences in median pre-operative calcitonin (513.5 vs. 1148.0 pg/mL, p = 0.101), tumor size (24.5 vs. 22.5 mm, p = 0.301), or LN involvement (41.7% vs. 61.5%, p = 0.307) between hereditary and sporadic MTC. Long-term outcomes were also comparable, with no differences in biochemical status, need for repeat surgery or residual/recurrent structural disease. Conclusion Hereditary MTC presents earlier and is more frequently detected due to screening, whereas sporadic MTC often presents symptomatically. Long-term outcomes are not primarily determined by hereditary status alone. Early access to RET mutation testing with a view to initiating prophylactic treatments rather than post detection surgery may improve disease burden.
Thyroid Neoplasms ; Cohort Studies

Introduction: Accurate diagnosis of thyrotoxicosis, a condition resulting from excessive thyroid hormone activity, is essential for appropriate management. However, access to diagnostic tools such as thyrotropin receptor antibody (TRAb) assays and thyroid ultrasonography remains limited in resource-constrained settings, highlighting the need for cost-effective alternatives. Recent studies suggest that the free triiodothyronine to free thyroxine (FT3/FT4) ratio may serve as a potential biomarker for differentiating the causes of thyrotoxicosis. Methodology: This cross-sectional study evaluated the FT3/FT4 ratio in newly diagnosed thyrotoxicosis patients aged ≥18 years recruited from Hospital Tengku Ampuan Rahimah, Hospital Banting, Klinik Kesihatan Pelabuhan Klang, and Klinik Kesihatan Pandamaran between February and December 2025. All participants underwent thyroid function testing (FT3, FT4, and TSH) and autoantibody assessment (TRAb and anti-thyroid peroxidase [anti-TPO]). Diagnostic performance of the FT3/FT4 ratio for Graves’ disease was assessed using receiver operating characteristic (ROC) curve analysis. Results: Fifty-eight patients were included, of whom 58.6% were diagnosed with Graves’ disease. Patients with Graves’ disease had significantly higher FT3 levels (median 16.8 pmol/L; IQR 10.9–25.7) compared to those with non-Graves’ thyrotoxicosis (median 8.3 pmol/L; IQR 5.3–13.5; p <0.001), with similar trends observed for FT4 levels (p <0.001). However, the FT3/ FT4 ratio did not differ significantly between groups (p >0.05), with an overall ROC AUC of 0.572, indicating poor discriminatory ability. Subgroup analysis based on FT4 levels improved performance; at FT4 <30 pmol/L, the FT3/FT4 ratio demonstrated 75.0% sensitivity, 91.7% specificity, and 87.5% diagnostic accuracy at a cutoff of 0.3445 (AUC = 0.813; 95% CI: 0.570–1.000; p = 0.069). No significant association was observed between the FT3/FT4 ratio and TRAb or anti-TPO. Conclusion The FT3/FT4 ratio has limited overall diagnostic utility but may provide adjunctive value in selected biochemical contexts, particularly in settings with limited access to immunological testing.
Diagnosis, Differential ; Thyroxine ; Triiodothyronine ; Thyrotoxicosis ; Cross-Sectional Studies

Introduction: The thyroid-kidney axis represents a clinically significant bidirectional relationship. Nephrotic syndrome (NS) may induce hypothyroidism via urinary hormonal and binding protein losses, while severe hypothyroidism may mimic NS and contribute to renal dysfunction. Cases: A 64-year-old male with gout, presented with facial puffiness, pedal edema, weight gain and frothy urine. Investigations revealed severe hypothyroidism FT4 <0.5 pmol/L (12–22 pmol/L) TSH 314 mIU/L (0.27–4.2 mIU/L) with NS – UPCR 7.7 3 g/L (0.04–0.15 g/L), albumin 22 g/L, total cholesterol 15.9 mmol/L – and renal impairment (eGFR 58 mL/min/1.73 m²). Positive anti-TPO antibodies suggested Hashimoto’s thyroiditis. He was initiated on liothyronine, hydrocortisone, levothyroxine and diuretics. Although FT4 normalized (14.4 pmol/L) a month later, renal function worsened requiring dialysis. Further evaluation including renal biopsy demonstrated IgA nephropathy as the underlying cause of NS and renal failure. Treatment with prednisolone led to gradual improvement in renal function and proteinuria (UPCR 0.21 g/L). A 73-year-old male with hypothyroidism diagnosed 6 months prior (FT4 11.9 pmol/L, TSH 7.23 mIU/L) for thyroxine replacement, diabetes, hypertension, dyslipidemia and CKD presented with anasarca, decompensated heart failure, pleural and pericardial effusions requiring ventilatory and inotropic support. On admission, he had marked hypothyroidism (FT4 2.9 pmol/L and TSH 97.2 mIU/L) and moderate proteinuria (UPCR 0.81 g/L). He was similarly treated with liothyronine, hydrocortisone and levothyroxine. Renal function initially deteriorated (creatinine 439 µmol/L, eGFR 11 mL/min/1.73 m²) but later returned to baseline with clinical recovery. Despite normalization of FT4 months later, proteinuria persisted; but renal function remained stable. Conclusion These cases highlight the overlapping manifestations of severe hypothyroidism and renal dysfunction with proteinuria. Each may mimic or exacerbate the other. NS may unmask underlying hypothyroidism. While inadequately treated hypothyroidism can worsen proteinuric CKD exacerbating hypothyroidism. Concurrent evaluation of both systems is essential to prevent misdiagnosis and guide timely management.
Hypothyroidism ; Proteinuria ; Kidney

Introduction: Parathyroid carcinoma is a rare endocrine malignancy found in 1–5% of patients with primary hyperparathyroidism. It commonly presents with severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. We report a challenging case of parathyroid carcinoma presenting with refractory hypercalcemia with incidental papillary thyroid microcarcinoma. Case: A 63-year-old female with hypertension, diabetes mellitus, dyslipidemia, and ischemic heart disease had been followed for primary hyperparathyroidism since 2014 (PTH5.5 pmol/L, calcium range 2.3–4.7 mmol/L). Initial neck ultrasound was suggestive of parathyroid adenoma over left side, but parathyroid scintigraphy failed to localize a lesion. She refused surgical intervention initially until April 2025, then she later agreed. Re-evaluation prior to operation revealed PTH level 76 pmol/L, and repeated parathyroid scintigraphy showed mild sestamibi avid uptake on left thyroid nodule. While awaiting surgery, she was admitted with a hypercalcemic crisis (serum calcium 3.7–5.38 mmol/L), complicated with acute kidney injury. Repeated ultrasound neck revealed extrathyroidal lesion adjacent to inferior pole of left thyroid (1.6 × 1.7 × 1.2 cm). She required aggressive intravenous hydration, intravenous pamidronate, calcitonin, and Denosumab to optimize her calcium level peri-operatively. She underwent left neck exploration with en-bloc left inferior parathyroidectomy, left hemithyroidectomy, and central neck dissection in November 2025. Histopathological examination confirmed parathyroid carcinoma (pT3N1) with nodal metastasis (1/4 lymph nodes positive) and an incidental papillary thyroid microcarcinoma measuring 1 mm (pT1a). Conclusion This case highlights the challenges of perioperative hypercalcemia management in parathyroid carcinoma. Effective preoperative control often requires multiple treatment modalities. Severe refractory hypercalcemia and high PTH level should raise a high index of suspicion for malignancy. Early complete resection is the cornerstone of treatment and is associated with optimal outcomes.
Papillary Thyroid Microcarcinoma ; Calcium ; Parathyroid Neoplasms

Introduction: Medullary thyroid carcinoma (MTC) has the highest familial predisposition syndrome of any hereditary cancer syndrome. The most common subtype of hereditary MTC is multiple endocrine neoplasia type 2A (MEN2A), which is an autosomal dominant syndrome characterized by MTC, pheochromocytoma, and primary hyperparathyroidism (HPP). This study evaluates the genotypic distribution, phenotypic manifestations, and clinical characteristics of MEN2A within a retrospective MTC cohort. Methodology: A retrospective audit of MTC patients was conducted at a tertiary centre. Patients with clinically or genetically confirmed hereditary MTC were identified for further analysis. Electronic medical records were reviewed for demographic data, RET germline mutations, occurrence of pheochromocytoma and HPP, laterality of disease, and documented surgical interventions. Results: In all, 18 patients (31.6%) were classified as hereditary from a cohort of 57 patients with a median age at diagnosis of 29.2 years. Among genetically confirmed cases with available variant data (n = 11), mutations predominantly involved exon 11 codon 634 (90.9%, n = 10), including p.Cys634Arg (n = 4), p.Cys634Tyr, and p.Cys634Ser, with one codon 618 mutation. Extrathyroidal manifestations were common. Pheochromocytoma occurred in 50.0% (n = 9), of which 77.8% (n = 7) were bilateral. Most patients underwent adrenalectomy, including bilateral procedures in those with bilateral disease. HPP was identified in 44.4% (n = 8), managed with selective parathyroidectomy. Both pheochromocytoma and HPP were present in 22.2% (n = 4), while isolated MTC occurred in 27.8% (n = 5). Conclusion Hereditary MTC in our cohort is predominantly associated with high-risk codon 634 RET mutations and demonstrates substantial penetrance of pheochromocytoma and HPP. The high frequency of bilateral adrenal involvement highlights the importance of systematic biochemical surveillance and appropriately timed surgical management in MEN2A. A nationwide registry would be timely.
Humans ; Multiple Endocrine Neoplasia Type 2a ; Thyroid Neoplasms

Introduction: Thalassemia is a hemoglobin synthesis disorder associated with chronic anemia and transfusion-related iron overload, which predisposes patients to multiple endocrine complications. Iron deposition in the pituitary and gonads may result in growth hormone deficiency (GHD) and hypogonadism. Empty sella syndrome (ESS), characterized by herniation of the subarachnoid space into the sella turcica, may also contribute to hypopituitarism. The coexistence of thalassemia-related endocrinopathies, ESS, and autoimmune thyroid disease is rare and presents significant diagnostic complexity. Case: A 27-year-old female with transfusion-dependent thalassemia on deferiprone presented with secondary amenorrhea and short stature. Her height was 145 cm (below the target range of 140.5–157.5 cm), body mass index 17.3 kg/m², and Tanner stage M3P1. Laboratory evaluation revealed elevated thyroidstimulating hormone (10.92 mIU/L) with low-normal free thyroxine 4 (11.4 pmol/L), consistent with primary hypothyroidism. Thyroid ultrasound demonstrated features of chronic thyroiditis, and anti-thyroid peroxidase antibodies (8.18 IU/mL) supported a diagnosis of Hashimoto’s thyroiditis. Insulin-like growth factor-1 was markedly reduced (68 ng/mL), indicating GHD. Morning cortisol was within normal range (14.5 µg/dL). Gonadotropins were inappropriately low-normal (folliclestimulating hormone 7.42 mIU/mL, luteinizing hormone 11.41 mIU/mL) with low estradiol (26.49 pg/mL), suggesting hypogonadotropic hypogonadism. Skeletal survey showed thalassemia-related bone changes, including trabecular coarsening and metaphyseal widening, with a predicted adult height of 142.7 cm. Pituitary magnetic resonance imaging revealed an empty sella. Conclusion Thalassemia must be recognized not only as a primary hematologic condition but also as a complex multisystem disorder with profound endocrine implications. Furthermore, the co-occurrence of these conditions with rare manifestations such as ESS and Hashimoto’s thyroiditis underscores the diagnostic complexity faced by clinicians. Therefore, early detection and rigorous, regular endocrine screening are essential to optimize management strategies and improve the long-term quality of life for patients with thalassemia.
Empty Sella Syndrome ; Growth Hormone ; Thalassemia ; Thyroiditis

Introduction: Thyroid eye disease (TED) is a heterogeneous condition and the most common extrathyroidal manifestation of Graves’ disease. Although most cases are mild, disease progression may threaten vision and significantly impact quality of life. Methodology: We described four patients with active moderate-to-severe TED, highlighting their clinical characteristics, therapeutic approaches, and clinical outcomes. Results: Three males and one female patient were included in this descriptive study. Most were identified by the endocrine team. Their median age was 52.5 years (range 47–56 years). All patients had long-standing Graves’ disease (range 6–10 years). Two of them were active smokers. Their clinical activity score ranged from 3 to 5. Common presenting features included diplopia (60%), proptosis (60%), and ocular redness (60%). At the onset of active TED, all patients were euthyroid while receiving either antithyroid therapy or were maintained on stable levothyroxine following radioactive iodine treatment and thyroidectomy. Thyroid receptor autoantibodies were assessed in only two patients, with one elevated result. Orbital computed tomography, performed in 3 patients, demonstrated extraocular muscle enlargement consistent with TED, particularly involving the inferior and medial recti. All patients received standard-dose intravenous methylprednisolone (cumulative 3.5–4.5 g). They showed improvement in visual acuity following treatment, with partial improvement in ophthalmoplegia. Conclusion Clinical risk factors observed in this series were consistent with the literature. TED diagnosis relies heavily on recognition by the endocrine team, underscoring the importance of holistic Graves’ disease management. Highdose corticosteroids remain the mainstay of treatment in our setting, with generally favorable outcomes when timely multidisciplinary care is provided.
Graves Ophthalmopathy

Introduction: Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of langerin-positive histiocytes. Endocrine involvement most frequently manifests as central diabetes insipidus or secondary hypothyroidism, caused by infiltration of the hypothalamic-pituitary axis. Conversely, direct infiltration of the thyroid gland leading to primary hypothyroidism is an exceptionally rare clinical entity, particularly when presenting concurrently with central disease. Case: A 21-year-old female with known right otic and multisystem LCH presented with septic shock secondary to a right ear abscess accompanied by polyuria and polydipsia. Physical examination revealed a palpable goiter. Clinical and biochemical evaluation confirmed central diabetes insipidus with associated anterior hypopituitarism (low adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone). However, concurrent thyroid function tests demonstrated overt primary hypothyroidism, evidenced by an appropriately elevated thyroid-stimulating hormone (26.19 mIU/L) and low free T4 (5.47 pmol/L), rather than the anticipated secondary hypothyroidism. Neck ultrasound showed diffuse thyroid enlargement with heterogeneous echotexture. Crucially, anti-thyroid peroxidase and anti-thyroglobulin antibodies were both negative, rendering Hashimoto’s thyroiditis highly unlikely. Although the patient declined confirmatory fine-needle aspiration, the constellation of a palpable goiter, characteristic ultrasonographic findings, negative autoimmunity, and active multisystem disease strongly supported a diagnosis of direct histiocytic infiltration of the thyroid gland. She was initiated on appropriate glucocorticoid coverage and subsequent levothyroxine replacement, alongside systemic intravenous cytarabine. Conclusion This case highlights a rare, mixed endocrine profile in multisystem LCH, demonstrating that pituitary and direct end-organ infiltration can coexist. Hypothyroidism in LCH patients with established central diabetes insipidus should not be reflexively assumed to be central in origin. A comprehensive diagnostic workup, including autoantibody screening, ultrasound, and ideally histopathological confirmation, is essential to accurately identify primary endocrine failure and guide appropriate clinical management in these complex cases.
Histiocytosis, Langerhans-Cell ; Hypothyroidism ; Pituitary Gland

Introduction: Painful Hashimoto's thyroiditis is a rare and atypical form of autoimmune thyroid disease characterized by thyroid pain and tenderness. It can closely resemble subacute thyroiditis and must be distinguished from other causes of thyroid pain, including hemorrhage into a cyst and thyroid abscess. This distinction is particularly important in pregnancy, where radionuclide imaging is not recommended. Case: A 27-year-old pregnant female (G4P3) at 24 weeks’ gestation, with Southeast Asian ovalocytosis and dietcontrolled gestational diabetes, was diagnosed with primary hypothyroidism at 14 weeks following evaluation of a painless goiter. Initial tests showed markedly elevated thyroid-stimulating hormone (>150 mIU/L), low free thyroxine (3.5 pmol/L), and positive anti-thyroid peroxidase antibodies (319 IU/mL), consistent with Hashimoto's thyroiditis. Levothyroxine therapy achieved biochemical euthyroidism. At 24 weeks, she developed acute right-sided anterior neck pain radiating to the ear, with dysphagia, odynophagia, and fever. Examination revealed a tender thyroid without lymphadenopathy. Ultrasound demonstrated diffuse enlargement with bilateral ill-defined hypoechoic avascular areas. Inflammatory markers showed markedly elevated C-reactive protein (184 mg/L) with a normal erythrocyte sedimentation rate (16 mm/h), while thyroid function remained within target range. Imaging and clinical findings made abscess and hemorrhage unlikely. The presence of pre-existing autoimmune thyroid disease, antibody positivity, and hypothyroidism before symptom onset supported painful Hashimoto's thyroiditis over subacute thyroiditis. This case highlights that normal thyroid function tests do not necessarily indicate disease remission, as inflammatory activity may persist independently of hormone levels. Conclusion Painful Hashimoto's thyroiditis should be considered in pregnant patients with known autoimmune thyroid disease presenting with acute thyroid pain despite normal thyroid function. Diagnosis requires integration of clinical, biochemical, and imaging findings to guide appropriate management.
Female ; Pregnancy ; Thyroiditis, Subacute