Atypical Primary Hyperparathyroidism in a Young Adult: Diagnostic and Management Challenges

Abstract

A 28-year-old male presented with recurrent fatigue, musculoskeletal pain, and nephrolithiasis over an 18-month period. Initial evaluations were inconclusive, with fluctuating calcium levels and nonspecific symptoms leading to delayed diagnosis. Subsequent biochemical workup revealed elevated parathyroid hormone (PTH) levels with intermittently normal serum calcium, raising suspicion of atypical primary hyperparathyroidism. Imaging studies demonstrated a solitary parathyroid adenoma. The patient underwent successful focused parathyroidectomy with normalization of biochemical parameters and resolution of symptoms. This case underscores the diagnostic complexity of atypical primary hyperparathyroidism in young adults and highlights the importance of high clinical suspicion, targeted investigations, and timely surgical intervention.

Introduction

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by inappropriate overproduction of parathyroid hormone, leading to disturbances in calcium and bone metabolism. While PHPT typically affects older adults, its occurrence in young individuals is uncommon and often presents atypically. Normocalcemic or intermittently hypercalcemic presentations may obscure diagnosis, resulting in prolonged morbidity. Early recognition is critical to prevent long-term complications involving the skeletal, renal, and neuropsychiatric systems. This case illustrates the diagnostic challenges and management considerations of atypical PHPT in a young adult.

Patient Information

Age / Gender: 28-year-old male
Occupation: Software engineer
Medical History: Recurrent renal calculi, episodic fatigue
Surgical History: None
Family History: No known endocrine or calcium disorders
Social History: Non-smoker, occasional alcohol consumption
Medications: Intermittent NSAIDs for musculoskeletal pain
Chief Complaints: Chronic fatigue, diffuse bone pain, and recurrent kidney stones over 18 months

Clinical Findings

General Examination: Mild dehydration, no neck masses
Musculoskeletal Examination: Diffuse bone tenderness without deformity
Renal Examination: No palpable masses
Neurological Examination: Normal cognitive function
Initial Impression: Metabolic etiology suspected due to multisystem involvement

Timeline

Month 0: First episode of renal colic; treated symptomatically
Month 6: Recurrent fatigue and musculoskeletal pain
Month 9: Second episode of nephrolithiasis
Month 12: Mild hypercalcemia noted, attributed to dehydration
Month 15: Persistently elevated PTH identified
Month 18: Imaging confirms parathyroid adenoma
Month 19: Surgical intervention performed
Month 20: Symptomatic and biochemical improvement noted

Diagnostic Assessment

Laboratory Investigations:

• Serum calcium: Intermittently high-normal to mildly elevated
• Parathyroid hormone: Persistently elevated
• Vitamin D: Mild deficiency
• Renal function: Normal
• Urinary calcium excretion: Elevated

Imaging:

• Neck ultrasound: Hypoechoic lesion inferior to left thyroid lobe
• Sestamibi scan: Focal uptake consistent with parathyroid adenoma

Diagnosis: Atypical primary hyperparathyroidism with intermittent hypercalcemia

Differential Diagnosis

• Familial hypocalciuric hypercalcemia
• Secondary hyperparathyroidism
• Vitamin D deficiency
• Malignancy-associated hypercalcemia
• Granulomatous disease

These were excluded based on biochemical profiles, imaging, and clinical context.

Therapeutic Intervention

Step 1 – Conservative / Initial Management

Hydration optimization and correction of vitamin D deficiency were initiated; however, symptoms persisted.

Step 2 – Preoperative Optimization

• Calcium and vitamin D levels optimized
• Renal function stabilized
• Endocrinology and surgical counseling provided

Step 3 – Surgical Intervention

Procedure: Focused parathyroidectomy
Anesthesia: General anesthesia
Intraoperative Notes:

• Single adenoma excised
• Intraoperative PTH levels dropped by >50%
• No complications encountered

Step 4 – Postoperative Management

• Calcium monitoring for hungry bone syndrome
• Oral calcium supplementation initiated
• Regular biochemical follow-up scheduled

Challenges Faced

• Atypical biochemical presentation with fluctuating calcium
• Delayed recognition due to young age
• Need to differentiate from secondary causes
• Patient anxiety regarding surgery and long-term outcomes

Follow-Up and Outcomes

Day 1: Transient hypocalcemia managed conservatively
Week 2: Resolution of bone pain and fatigue
Month 1: Normal calcium and PTH levels
Month 3: No recurrence of nephrolithiasis
Month 6: Sustained biochemical remission and improved quality of life

Discussion

Atypical primary hyperparathyroidism poses significant diagnostic challenges, particularly in young adults, where classical and sustained hypercalcemia may be absent or only intermittently present. In such cases, patients often exhibit normocalcemic or fluctuating biochemical profiles, which can obscure the underlying endocrine pathology and lead to delayed recognition. As a result, symptoms such as chronic fatigue, diffuse musculoskeletal pain, neurocognitive disturbances, or recurrent nephrolithiasis may be attributed to more common or benign conditions, further postponing definitive diagnosis and treatment.

The absence of overt hypercalcemia underscores the critical importance of serial biochemical monitoring. Repeated assessments of serum calcium, parathyroid hormone levels, vitamin D status, and urinary calcium excretion are essential to identify inappropriate PTH elevation and to distinguish atypical primary hyperparathyroidism from secondary hyperparathyroidism, vitamin D deficiency, or inherited calcium-sensing receptor disorders. Early biochemical trends, rather than isolated laboratory values, often provide the most reliable diagnostic clues in younger patients.

Failure to recognize atypical PHPT in a timely manner can result in progressive renal and skeletal complications, including recurrent kidney stone formation, reduced bone mineral density, and increased fracture risk at a relatively young age. These complications carry long-term consequences that may persist even after biochemical correction. Therefore, clinicians should maintain a low threshold for considering PHPT in young individuals with unexplained nephrolithiasis, persistent bone pain, or metabolic abnormalities that do not respond to standard interventions.

Surgical excision of the hyperfunctioning parathyroid tissue remains the definitive treatment and is associated with excellent biochemical normalization and symptomatic improvement when performed at the appropriate stage. Early surgical intervention not only alleviates current symptoms but also prevents irreversible end-organ damage, reinforcing the value of early diagnosis and proactive management in atypical presentations of primary hyperparathyroidism.

Multidisciplinary Approach

Endocrinologist: Hormonal evaluation and diagnosis
Endocrine Surgeon: Parathyroidectomy
Radiologist: Localization imaging
Nephrologist: Renal complication management
Nursing Staff: Perioperative care
Pharmacist: Calcium and vitamin D supplementation guidance

Key Takeaways

• Primary hyperparathyroidism can present atypically in young adults
• Normal or fluctuating calcium levels do not exclude PHPT
• Persistent PTH elevation warrants thorough evaluation
• Surgery is curative in most cases
• Early diagnosis prevents long-term complications

Patient’s Perspective

“I struggled for years with unexplained pain and kidney stones. After surgery, my energy levels improved, and the pain disappeared. I finally feel healthy again.”

Conclusion

This case highlights the complexities involved in diagnosing atypical primary hyperparathyroidism in young adults, a population in which the condition is often overlooked due to its rarity and frequently non-classical presentation. Unlike the traditional form of primary hyperparathyroidism seen in older individuals with overt hypercalcemia, younger patients may present with subtle, fluctuating, or even normal serum calcium levels. This biochemical variability can lead to diagnostic delays, misattribution of symptoms, and prolonged patient morbidity. Consequently, clinicians must maintain a high index of suspicion when encountering young adults with recurrent nephrolithiasis, unexplained musculoskeletal pain, chronic fatigue, or neurocognitive complaints, even in the absence of persistent hypercalcemia.

A comprehensive biochemical assessment plays a pivotal role in early detection. Serial measurements of serum calcium, parathyroid hormone levels, vitamin D status, and urinary calcium excretion are essential to distinguish atypical primary hyperparathyroidism from secondary causes and inherited disorders. Targeted imaging modalities, including high-resolution neck ultrasonography and sestamibi scintigraphy, further support accurate localization and surgical planning. Early and precise diagnosis enables timely intervention, preventing progressive skeletal demineralization, renal impairment, and long-term cardiovascular or neuropsychiatric sequelae.

Surgical management remains the definitive and curative treatment for primary hyperparathyroidism, even in atypical cases. Focused parathyroidectomy, guided by accurate localization and intraoperative hormone monitoring, offers excellent biochemical and symptomatic outcomes with minimal morbidity. Importantly, early recognition and intervention reduce the risk of irreversible complications and significantly improve quality of life.

Finally, multidisciplinary collaboration among endocrinologists, surgeons, radiologists, nephrologists, and allied healthcare professionals is fundamental to optimizing patient outcomes. A patient-centered approach that emphasizes education, shared decision-making, and long-term follow-up ensures sustained biochemical control, symptom resolution, and overall functional recovery.

References

• Endocrine Society Clinical Practice Guidelines
• NIH Consensus Development Conference on Hyperparathyroidism
• Bilezikian JP. Primary Hyperparathyroidism: Clinical and Management Perspectives
• NEJM. Advances in Parathyroid Surgery and Imaging

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