A 37-year-old recreational runner presented with progressive left shin pain while training for a half marathon.
At first glance, this looked like a familiar overuse presentation, a runner who had increased training load in preparation for an event and developed focal tibial pain. What made the case more interesting was the wider history.
Alongside the expected training story sat a cluster of subtle systemic symptoms: increased thirst, waking to pass urine, fatigue and a sense that his mood had become noticeably flatter over recent months.
The final diagnosis was a posteromedial tibial bone stress injury occurring in the context of newly diagnosed primary hyperparathyroidism, due to a parathyroid adenoma.
Case Presentation – Clinical history
The patient was a 37-year-old man working in consulting, with no significant past medical history and no regular medication. He had entered a local half marathon and had been following an online training plan for approximately 10 weeks.
His weekly running volume had increased from around 20 km per week to approximately 50 km per week. Over the same period, he had added a weekly interval session and a longer weekend run, while continuing to do most of his running on pavement.
He described himself as generally sensible with training, but admitted that the closer the event got, the more reluctant he was to miss sessions.
He initially noticed a mild ache over the medial aspect of the left shin after a longer run. Over the following 2 to 3 weeks, the pain became more localised and more predictable.
At first, it was present only during running, then earlier in runs, then during brisk walking, and by the time he presented it was also noticeable on stairs and after prolonged standing.
There had been no single traumatic event.
What shifted the consultation was the wider review of systems.
On questioning, he reported:
- Increased thirst over several months
- Waking twice at night to pass urine
- Fatigue that felt ‘out of proportion’ to training
- A flattening in mood and increased irritability
- No history of renal colic or known kidney stones
- No known previous fractures
- No disordered eating, weight loss, gastrointestinal symptoms
Past medical history
- No significant past medical history.
- No previous bone stress injury
- No corticosteroid exposure
- No smoking history
- Alcohol minimal
Exercise history
- Recreational runner, usually 2 to 3 runs per week
- First formal half-marathon training block
- Intermittent gym work, but no consistent lower-limb strength programme in the previous 6 months
Nutrition
- No deliberate restriction
- Reasonable calorie intake by history
- No major recent weight change
Family history
- No known metabolic bone disease
- No family history of recurrent hypercalcaemia
- No known family history of recurrent renal stones or endocrine syndromes
Clinical examination
- He walked with a mildly antalgic gait.
- Lumbar spine movements were full and non-provocative.
- The knee and ankle examinations were otherwise unremarkable.
- There was focal tenderness over the posteromedial border of the distal tibia.
- Resisted ankle movements did not reproduce significant symptoms.
- Single-leg loading reproduced local tibial pain.
- The pain was more focal and load-related than would be typical for a straightforward medial tibial stress syndrome presentation.
- There were no features to suggest an acute calf tear, vascular problem or referred lumbar pain.
Differential diagnosis
The main differential diagnoses at presentation were:
1. Posteromedial tibial bone stress injury
Most likely given the focal tibial tenderness, progressive pain pattern, clear relationship to impact loading, and recent increase in running volume.
2. Medial tibial stress syndrome
A reasonable consideration, but the symptoms were more focal, more progressively load-intolerant, and less diffuse than would be expected for a typical MTSS presentation.
3. Soleus or deep posterior compartment musculotendinous overload
Possible, though the tenderness and symptom behaviour were more bony than soft-tissue dominant.
4. Chronic exertional compartment syndrome
Less likely because the pain did not present as a predictable tightness resolving rapidly after exercise cessation, and there were no neurological symptoms.
5. Referred pain from lumbar or other proximal sources
Considered lower on the list given the highly localised tibial symptoms and non-provocative spinal examination.
Imaging and investigations
Fig 1
Bilateral TSI: grade 3 TSI on the left and grade 1 on the right. Left-sided periosteal and bone marrow oedema with cortical abnormalities on medio-posterior side. Subtle periosteal oedema on the right side in the same localisation
Fig 2
The same patient. Note that periosteal oedema is usually more extensive than changes in cortex
Fig 3
The same patient with grade 3 TSI-periosteal oedema with discrete bone marrow oedema. Arrows show thickened cortex with loss of cortical signal void (ax PD fatsat, T1 fatsat, T1)
MRI demonstrated a posteromedial tibial bone stress injury with periosteal and marrow oedema, without anterior cortical involvement or features of a high-risk anterior cortex lesion.
Plain radiographs are often unrevealing early in bone stress injury, and MRI is commonly used to confirm the diagnosis and define the grade and location of injury.
At this point the musculoskeletal diagnosis was established. However, the consultation did not comfortably end at ‘training error’ because the history contained additional features suggestive of hypercalcaemia.
A broader bone health and metabolic work-up was therefore arranged.
Blood tests and endocrine work-up
Initial blood tests showed:
- Albumin-adjusted calcium: 2.86 mmol/L
- Repeat albumin-adjusted calcium: 2.88 mmol/L
- PTH: 10.2 pmol/L
- Phosphate: 0.72 mmol/L
- ALP: mildly elevated
- 25-OH vitamin D: 41 nmol/L
- Renal function: normal
The initial workup demonstrated a biochemical hyperparathyroidism, repeated hypercalcaemia with an inappropriately elevated PTH.
Further endocrine investigations showed:
- 24-hour urinary calcium excretion: not low, arguing against familial hypocalciuric hypercalcaemia
- DXA scan: bone mineral density below expected range for age, most marked at the distal radius
- Renal tract ultrasound: no renal stones or nephrocalcinosis
- Neck ultrasound: likely parathyroid adenoma
- Sestamibi scan: concordant uptake in the adenoma location
1a-c: 99m Tc-sestamibi scan showing: (a) right inferior parathyroid adenoma
Mantar F, Gunduz S, Gunduz U. A reference finding rarely seen in primary hyperparathyroidism: Brown tumor. Case Rep Med. 2012;2012:432676. doi:10.1155/2012/432676
Differential diagnosis of hypercalcaemia in this case
When hypercalcaemia is identified, the most useful first step is to decide whether it is PTH-dependent or PTH-independent.
In this patient, the PTH was inappropriately elevated in the presence of repeated hypercalcaemia, which makes a PTH-dependent cause the key branch point. The main differentials in that setting are primary hyperparathyroidism and familial hypocalciuric hypercalcaemia (FHH). Tertiary hyperparathyroidism would be much less likely here because there was no history of chronic kidney disease or longstanding secondary hyperparathyroidism, and lithium-associated hypercalcaemia was not supported by the medication history.
By contrast, PTH-independent hypercalcaemia usually suppresses PTH and includes causes such as malignancy-associated hypercalcaemia, vitamin D-mediated hypercalcaemia, granulomatous disease, thyrotoxicosis, adrenal insufficiency, immobilisation, and medication-related causes such as thiazides or excess calcium intake.
In this case, those alternatives were less convincing because the biochemical pattern showed repeated hypercalcaemia with an inappropriately elevated PTH, low phosphate, urinary calcium that was not low, normal renal function, concordant localisation imaging, and subsequent normalisation of calcium after parathyroidectomy.
Taken together, that pattern is most consistent with primary hyperparathyroidism due to a solitary parathyroid adenoma.
Physiology of calcium homeostasis
Calcium homeostasis is maintained through coordinated regulation between the parathyroid glands, kidneys, gastrointestinal tract and skeleton. Extracellular calcium is sensed by receptors on the parathyroid glands. When serum calcium falls, PTH secretion increases. PTH then acts at the kidney to increase calcium reabsorption and reduce phosphate reabsorption, and it stimulates renal 1-alpha-hydroxylase, increasing conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol). Calcitriol in turn increases intestinal calcium absorption, while PTH also promotes mobilisation of calcium from bone.
In primary hyperparathyroidism, this feedback loop becomes dysregulated because PTH secretion is relatively autonomous and is no longer appropriately suppressed by hypercalcaemia. The consequence is persistent calcium release from bone, increased renal calcium conservation, increased calcitriol production, and increased gastrointestinal calcium absorption. Even though PTH increases tubular calcium reabsorption, the filtered calcium load is often high enough that urinary calcium excretion still rises, which helps explain the association with renal stones. Skeletally, chronic excess PTH has a particularly important effect on cortical bone, so reduced bone density at sites such as the distal radius is a classic pattern. In an active person, that reduction in skeletal resilience may lower the threshold at which an otherwise familiar training-load problem becomes a clinically significant bone stress injury.
Final diagnosis
Posteromedial tibial bone stress injury in a runner, with underlying primary hyperparathyroidism, biochemically confirmed and localised pre-operatively to a parathyroid adenoma.
The tibial bone stress injury was the presenting sports medicine problem, but the wider diagnosis explained why bone resilience may have been reduced.
In hindsight, the thirst, urinary frequency, fatigue and mood change were not incidental details: they were the clues that widened the case beyond simple load management.
Management
1. Sports medicine and rehabilitation management
Because this was a low-risk posteromedial tibial bone stress injury, management was non-operative.
He was advised to stop running and impact exercise immediately, but he did not require prolonged non-weight-bearing.
Walking volume was temporarily reduced to a pain-controlled level, and cross-training was maintained using non-impact modalities.
Physiotherapy focused on:
- Education regarding relative rest and symptom-guided loading
- Maintaining conditioning without impact
- Calf, soleus, gluteal and trunk strength
- Lower-limb load tolerance and gradual progression of walking
- Later, a structured return-to-run programme once symptoms had settled
2. Endocrine management
He was referred to endocrinology and then to for surgical management. His vitamin D insufficiency was addressed cautiously under endocrine supervision, and hydration advice was reinforced.
Because surgery was appropriate and feasible, there was no indication to use cinacalcet as primary treatment.
Cnacalcet is typically used for selected cases when surgery is unsuccessful, unsuitable or declined. Bisphosphonates may be considered for fracture risk reduction but should not routinely used to treat the chronic hypercalcaemia itself.
The patient underwent a focused parathyroidectomy after concordant ultrasound and sestamibi localisation.
Histology confirmed a benign parathyroid adenoma.
Outcome
At 6 weeks, he was walking comfortably with no day-to-day tibial pain. He then progressed through a graded reloading programme, beginning with brisk walking and low-impact conditioning before starting a structured walk-jog progression.
Discussion
For healthcare professionals, the value of this case is in recognising when a common injury pattern contains uncommon clues.
Most tibial bone stress injuries in runners will be explained by some combination of training load, tissue capacity, surface, recovery, biomechanics, fuelling or bone health factors such as low energy availability. But occasionally the history does not sit comfortably within a purely mechanical story.
In this case, the crucial clue was not one dramatic red flag. It was a cluster of mild systemic features in an active person preparing for an event. None is diagnostic in isolation. Together, however, they were enough to justify widening the differential and arranging medical follow-up.
Key Summary and Learning Points
- Tibial bone stress injury is a common running-related diagnosis, and the posteromedial tibial shaft is generally a low-risk site compared with high-risk locations such as the anterior tibial cortex, navicular or femoral neck.
- Not every bone stress injury is just a training-load problem. Ask about systemic symptoms such as thirst, polyuria, fatigue, low mood and renal stone history.
- In suspected primary hyperparathyroidism, the UK pathway includes repeat albumin-adjusted calcium, concurrent PTH, vitamin D assessment, and urinary calcium testing to help exclude familial hypocalciuric hypercalcaemia.
- NICE recommends referral for parathyroid surgery when primary hyperparathyroidism is confirmed and there are symptoms of hypercalcaemia, end-organ disease, or albumin-adjusted calcium of 2.85 mmol/L or above.
Selected references
3. Shaker JL, Deftos L. Calcium and Phosphate Homeostasis. Endotext [Internet]. 2023.
4. Helbing A, et al. Primary Hyperparathyroidism. StatPearls [Internet]. 2024.
