Study analysis · International Journal of Circumpolar Health · 2002
A woman with a rare genetic syndrome that causes jaw tumors and overactive parathyroid glands also developed a rare adrenal disease that secretes two hormones at once—could one mutation be to blame?
A single case suggests that a mutation in the CDC73 gene, known for causing hyperparathyroidism-jaw tumor syndrome, might also lead to a rare adrenal condition called primary bilateral macronodular adrenal hyperplasia.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
In simple terms
This study is like a single story about one person. It can't prove that anything causes anything else. It only gives us clues that scientists might want to study later with better methods.
What’s the bottom line?
Scientists followed winter swimmers and non-swimmers from autumn to spring to see if cold-water swimming changes blood pressure or stress hormones.
How strong is this study?
The study is very weak because it only looks at one person and has no comparison group. That means we can't trust the results to say anything about people in general. We need much larger studies with control groups to know for sure.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
0 / 100
- Randomizationnot randomized
- Blindingblinding unclear
- Control groupno control group
- Sample size (n=1)+0.1/20
- Follow-upno follow-up reported
100 / 100
0 / 100
- P-valuesno p-values reported
- Effect sizeno effect size reported
- Confidence intervalsno confidence intervals
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 528 / 100
Probability of being correct
Snapshots of a population at a single point in time, or descriptions of small groups. Can identify correlations and prevalence, but cannot determine cause and effect.
This design cannot establish causation — the findings describe an association, not a cause. This is a case report/series with a sample size of 1, no control group, no randomization, and no blinding. Any observed changes could be due to natural history, seasonal variation, placebo effect, or confounding. Cause-effect relationships cannot be established.
No Conflicts
No conflicts of interest identified
No conflicts identified; all listed authors declared no disclosures.
This is a case report abstract. A disclosure statement is present and all authors report 'None' for conflicts of interest. No funding statement is included.
Key takeaways
- 01
Winter swimmers' systolic blood pressure dropped from 134 to 128 mmHg (absolute 6 mmHg lower), but non-swimmers also dropped a bit.
- 02
Noradrenaline fell in both groups, a bit more in swimmers, but not significantly different.
- 03
Serotonin fell by about 50% relative in both groups.
- 04
HVA and beta-endorphin stayed the same.
- 05
Some weak correlations with mood were found.
- 06
The blood pressure drop in swimmers was small (6 mmHg) and also happened in non-swimmers, so it's probably not specific to winter swimming.
- 07
The absolute changes in hormones were not reported for serotonin, but the relative drop was similar in both groups.
- 08
Overall, this small study suggests winter swimming doesn't have a clear special effect on these markers beyond normal seasonal changes.
Surprising findings
- CDC73 mutation, typically linked to parathyroid and jaw tumors, may also predispose to PBMAH.PBMAH is usually associated with ARMC5, MEN1, or other genes; CDC73 has never been implicated before.
- The patient had no jaw tumor despite having HPT-JT syndrome.The syndrome is named for jaw tumors, so their absence is counterintuitive.
- The CDC73 mutation was found only in 2024, over a decade after the patient first presented with adrenal nodules.It shows how genetic diagnosis can lag behind clinical manifestations.
Practical takeaways
Clinicians should consider genetic testing for CDC73 in patients with PBMAH who also have features of HPT-JT, such as hyperparathyroidism or renal stones.
This is based on a single case; causality is not proven. Most PBMAH is not caused by CDC73.
low confidencePatients with HPT-JT should be monitored for adrenal function and morphology, as they may develop PBMAH.
The frequency of this complication is unknown; routine screening may not be cost-effective.
low confidenceFor patients with co-secreting adrenal nodules, consider aberrant hormone regulation (e.g., vasopressin, posture, 5-HT4R agonists) when interpreting dynamic tests.
This is a technical point for endocrinologists; management remains individualized.
medium confidenceWhy this study matters
First Reported Case Linking CDC73 to Adrenal Hyperplasia
A 54-year-old woman with hyperparathyroidism-jaw tumor syndrome (HPT-JT) due to a CDC73 mutation was found to have primary bilateral macronodular adrenal hyperplasia (PBMAH) that co-secreted cortisol and aldosterone. Genetic testing ruled out common PBMAH genes like ARMC5 and MEN1, pointing to CDC73 as a possible new culprit.
It expands the known effects of a single gene mutation, potentially changing how we screen patients with HPT-JT.
Co-secretion of Two Hormones from Adrenal Nodules
The patient's adrenal nodules produced both cortisol (causing weight gain, fatigue, myopathy) and aldosterone (causing hypertension and sleep apnea). Dynamic testing showed aberrant regulation by vasopressin, upright posture, and 5-HT4R agonists.
Most adrenal tumors secrete one hormone; co-secretion is rare and complicates diagnosis and treatment.
A 30-Year Journey to Diagnosis
The patient had recurrent kidney stones since age 19, three parathyroidectomies at ages 26, 46, and 53 for severe hyperparathyroidism, and developed PBMAH by age 54. The CDC73 mutation was only identified in 2024, after 11 years of follow-up.
Highlights the importance of long-term monitoring and genetic testing in rare syndromes.
No Jaw Tumor, But Still HPT-JT
Despite the syndrome's name, the patient had no jaw tumor at recent imaging. This shows that not all features of a genetic syndrome appear in every patient.
Challenges the assumption that a syndrome's namesake symptoms are always present.
Want the whole report?
Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Scientists followed winter swimmers and non-swimmers from autumn to spring to see if cold-water swimming changes blood pressure or stress hormones.
Research results
Winter swimmers' systolic blood pressure dropped from 134 to 128 mmHg (absolute 6 mmHg lower), but non-swimmers also dropped a bit. Noradrenaline fell in both groups, a bit more in swimmers, but not significantly different. Serotonin fell by about 50% relative in both groups. HVA and beta-endorphin stayed the same. Some weak correlations with mood were found.
What this means - more context
The blood pressure drop in swimmers was small (6 mmHg) and also happened in non-swimmers, so it's probably not specific to winter swimming. The absolute changes in hormones were not reported for serotonin, but the relative drop was similar in both groups. Overall, this small study suggests winter swimming doesn't have a clear special effect on these markers beyond normal seasonal changes.
Follow-up observational study investigating blood pressure and hormonal changes during one winter swimming season in winter swimmers and non-swimmer controls, comparing humoral results to psychological traits.
Small observational study of winter swimmers and controls from autumn to spring. Mean systolic blood pressure in winter swimmers fell from 134 to 128 mmHg (absolute reduction 6 mmHg, p<0.05), but controls showed a similar non-significant drop. Noradrenaline decreased significantly from autumn to spring in both groups, more so in swimmers, but between-group differences were not statistically significant. Plasma serotonin decreased by about 50% relative in both groups. HVA and beta-endorphin remained unchanged. Weak-to-moderate correlations were found between HVA and blood pressure/anxiety, endorphin and hysteria, and 5-HIAA and obsessionality. No clear effect of winter swimming as such was detected.
Methods Used
Observational follow-up of winter swimmers and non-swimmer controls with blood sampling in autumn, winter, and spring; measured blood pressure, plasma catecholamines (noradrenaline, adrenaline), serotonin, 5-HIAA, HVA, beta-endorphin, and psychological traits.
Main Finding
Winter swimming did not produce a clear effect on blood pressure or plasma catecholamine levels beyond changes also seen in non-swimmers. The absolute systolic blood pressure reduction in swimmers was 6 mmHg (134 to 128 mmHg, p<0.05), but controls had a similar non-significant drop. Noradrenaline decreased significantly from autumn to spring in both groups, more so in swimmers, but between-group difference was not statistically significant. Serotonin decreased by about 50% relative in both groups. These findings suggest seasonal variation or adaptation to measurement rather than a specific effect of winter swimming.
Confidence Level
Low. Small sample, uncontrolled (non-randomized), no blinding, multiple comparisons, and no statistically significant between-group differences. Findings are hypothesis-generating only. Not retracted; no corrections reported.
Study Flags
Red Flags
- •Small sample size
- •No randomization or blinding
- •Multiple comparisons and no significant between-group differences
Surprising Findings
CDC73 mutation, typically linked to parathyroid and jaw tumors, may also predispose to PBMAH.
PBMAH is usually associated with ARMC5, MEN1, or other genes; CDC73 has never been implicated before.
Practical Takeaways
Clinicians should consider genetic testing for CDC73 in patients with PBMAH who also have features of HPT-JT, such as hyperparathyroidism or renal stones.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 528 / 100
Probability of being correct
Snapshots of a population at a single point in time, or descriptions of small groups. Can identify correlations and prevalence, but cannot determine cause and effect.
Human Case Report
Subject
Lower probability
on the GRADE evidence scale
This study is like a single story about one person. It can't prove that anything causes anything else. It only gives us clues that scientists might want to study later with better methods.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Detailed clinical observation of a single case
- May generate hypotheses for future research
Weaknesses
- Sample size 1
- No control group
- No randomization
Methodology
Evidence Keywords
Statistical Reporting
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Scientists followed winter swimmers and non-swimmers from autumn to spring to see if cold-water swimming changes blood pressure or stress hormones.
Research results
Winter swimmers' systolic blood pressure dropped from 134 to 128 mmHg (absolute 6 mmHg lower), but non-swimmers also dropped a bit. Noradrenaline fell in both groups, a bit more in swimmers, but not significantly different. Serotonin fell by about 50% relative in both groups. HVA and beta-endorphin stayed the same. Some weak correlations with mood were found.
What this means - more context
The blood pressure drop in swimmers was small (6 mmHg) and also happened in non-swimmers, so it's probably not specific to winter swimming. The absolute changes in hormones were not reported for serotonin, but the relative drop was similar in both groups. Overall, this small study suggests winter swimming doesn't have a clear special effect on these markers beyond normal seasonal changes.
Follow-up observational study investigating blood pressure and hormonal changes during one winter swimming season in winter swimmers and non-swimmer controls, comparing humoral results to psychological traits.
Small observational study of winter swimmers and controls from autumn to spring. Mean systolic blood pressure in winter swimmers fell from 134 to 128 mmHg (absolute reduction 6 mmHg, p<0.05), but controls showed a similar non-significant drop. Noradrenaline decreased significantly from autumn to spring in both groups, more so in swimmers, but between-group differences were not statistically significant. Plasma serotonin decreased by about 50% relative in both groups. HVA and beta-endorphin remained unchanged. Weak-to-moderate correlations were found between HVA and blood pressure/anxiety, endorphin and hysteria, and 5-HIAA and obsessionality. No clear effect of winter swimming as such was detected.
Methods Used
Observational follow-up of winter swimmers and non-swimmer controls with blood sampling in autumn, winter, and spring; measured blood pressure, plasma catecholamines (noradrenaline, adrenaline), serotonin, 5-HIAA, HVA, beta-endorphin, and psychological traits.
Main Finding
Winter swimming did not produce a clear effect on blood pressure or plasma catecholamine levels beyond changes also seen in non-swimmers. The absolute systolic blood pressure reduction in swimmers was 6 mmHg (134 to 128 mmHg, p<0.05), but controls had a similar non-significant drop. Noradrenaline decreased significantly from autumn to spring in both groups, more so in swimmers, but between-group difference was not statistically significant. Serotonin decreased by about 50% relative in both groups. These findings suggest seasonal variation or adaptation to measurement rather than a specific effect of winter swimming.
Confidence Level
Low. Small sample, uncontrolled (non-randomized), no blinding, multiple comparisons, and no statistically significant between-group differences. Findings are hypothesis-generating only. Not retracted; no corrections reported.
Study Flags
Red Flags
- •Small sample size
- •No randomization or blinding
- •Multiple comparisons and no significant between-group differences
Surprising Findings
CDC73 mutation, typically linked to parathyroid and jaw tumors, may also predispose to PBMAH.
PBMAH is usually associated with ARMC5, MEN1, or other genes; CDC73 has never been implicated before.
Practical Takeaways
Clinicians should consider genetic testing for CDC73 in patients with PBMAH who also have features of HPT-JT, such as hyperparathyroidism or renal stones.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 528 / 100
Probability of being correct
Snapshots of a population at a single point in time, or descriptions of small groups. Can identify correlations and prevalence, but cannot determine cause and effect.
Human Case Report
Subject
Lower probability
on the GRADE evidence scale
This study is like a single story about one person. It can't prove that anything causes anything else. It only gives us clues that scientists might want to study later with better methods.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Detailed clinical observation of a single case
- May generate hypotheses for future research
Weaknesses
- Sample size 1
- No control group
- No randomization
Methodology
Evidence Keywords
Statistical Reporting
Scoring
How strong is this study?
The study is very weak because it only looks at one person and has no comparison group. That means we can't trust the results to say anything about people in general. We need much larger studies with control groups to know for sure.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
0 / 100
- Randomizationnot randomized
- Blindingblinding unclear
- Control groupno control group
- Sample size (n=1)+0.1/20
- Follow-upno follow-up reported
100 / 100
0 / 100
- P-valuesno p-values reported
- Effect sizeno effect size reported
- Confidence intervalsno confidence intervals
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 528 / 100
Probability of being correct
Snapshots of a population at a single point in time, or descriptions of small groups. Can identify correlations and prevalence, but cannot determine cause and effect.
This design cannot establish causation — the findings describe an association, not a cause. This is a case report/series with a sample size of 1, no control group, no randomization, and no blinding. Any observed changes could be due to natural history, seasonal variation, placebo effect, or confounding. Cause-effect relationships cannot be established.
No Conflicts
No conflicts of interest identified
No conflicts identified; all listed authors declared no disclosures.
This is a case report abstract. A disclosure statement is present and all authors report 'None' for conflicts of interest. No funding statement is included.
Standing
The people behind it
The researchers who wrote the study this analysis is built on.
Authored by
4 researchersIf this is your work, this is how we attribute it on Fit Body Science. Jorma Hirvonen is listed as the lead author.