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endo.hypopituitarism.core.v1

Hypopituitarism

endocrinologychronicsubacuteadultoutpatientinpatient
Start encounter →Print handoutPRODUCTION

PLACEHOLDER manifest — points at prisma/seed/manifests/endo.cushing_syndrome.v1.ts; a dedicated endo.hypopituitarism.core.v1 manifest is not yet authored (tracked in design-brief Open gaps). No problem-package folder yet under src/lib/tier3/problem-package/packages/ — design brief lives only at the dossier/brief level; atoms.* not authored. RxNav-deferred: NO RxNorm CUIs asserted anywhere in regimen_axes or setting_playbooks; rxcui validation via scripts/research/rxnav-validate.ts is a PRODUCTION-promotion prerequisite. Calculator inventory uses generic registry tools (calc.qsofa, calc.news2, calc.corrected_ca); a dedicated ITT/cosyntropin interpretation aid and copeptin-based DI calculator are not yet in clinical-tools-registry.ts. Bayesian likelihood ratios for central-rule lab interpretation (paired low hormone + inappropriately low/normal trophic hormone) to be wired in a later evidence pass.

Entry points (5)

  • imaging
    Pituitary / parasellar mass or stalk lesion on MRI (Fleseriu JCEM 2016 ES)
    sellar_parasellar_mass
  • lab_abnormality
    Low peripheral hormone with inappropriately low/normal trophic hormone (low cortisol + low/normal ACTH, low FT4 + low/normal TSH) (Fleseriu JCEM 2016 ES)
    central_hormone_pattern
  • symptom
    Fatigue, hypotension, amenorrhea/low libido, cold intolerance, polyuria after pituitary insult (Fleseriu JCEM 2016 ES)
    pituitary_failure_syndrome
  • history
    Sellar surgery / cranial RT / apoplexy / Sheehan / TBI-SAH / checkpoint-inhibitor exposure (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    pituitary_insult_history
  • problem_list
    Known hypopituitarism — under-replacement or intercurrent stress (Fleseriu JCEM 2016 ES)
    known_hypopituitarism

Required inputs (14)

  • agerequired
    demographic • used at CONTEXT
    GH replacement decision and sex-steroid targets are age-dependent; growth-axis irrelevant in older adults (Fleseriu JCEM 2016 ES)
  • sexrequired
    demographic • used at CONTEXT
    Gonadotropin-axis assessment and sex-steroid replacement differ by sex; pregnancy intent drives fertility-induction referral (Fleseriu JCEM 2016 ES)
  • sbprequired
    vital • used at RED_FLAGS
    Hypotension flags secondary adrenal insufficiency / impending adrenal crisis — the life-threatening axis (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
  • cortisolrequired
    lab • used at INITIAL_WORKUP
    0800 cortisol is the screening anchor for the ACTH axis; interpret by CENTRAL rules (paired with ACTH), never by primary-AI cutoffs alone (Fleseriu JCEM 2016 ES)
  • acthrequired
    lab • used at INITIAL_WORKUP
    Inappropriately low/normal ACTH with low cortisol defines SECONDARY adrenal insufficiency and separates this engine from primary adrenal failure (Fleseriu JCEM 2016 ES)
  • free_t4required
    lab • used at INITIAL_WORKUP
    Central hypothyroidism is diagnosed by LOW free T4 with low/normal TSH — TSH alone must NOT be used (Fleseriu JCEM 2016 ES; Persani JCEM 2018)
  • tshrequired
    lab • used at INITIAL_WORKUP
    TSH is inappropriately low/normal in central hypothyroidism; it is read only paired with free T4, never as a standalone screen (Persani JCEM 2018)
  • sodiumrequired
    lab • used at INITIAL_WORKUP
    Hyponatremia signals secondary AI, central hypothyroidism, or SIADH; hypernatremia + polyuria signals central DI (posterior axis) (Fleseriu JCEM 2016 ES)
  • prolactin
    lab • used at INITIAL_WORKUP
    Mild hyperprolactinemia (stalk effect/disconnection) vs low prolactin (gland destruction, Sheehan) localizes the lesion (Fleseriu JCEM 2016 ES)
  • igf1
    lab • used at BRANCHING_WORKUP
    IGF-1 screens the GH axis; low IGF-1 with multiple deficiencies supports GHD without provocative testing in some contexts (Yuen JCEM 2019 AACE/ACE GH)
  • mri_pituitaryrequired
    imaging • used at BRANCHING_WORKUP
    Dedicated sellar MRI defines tumor/parasellar mass, stalk thickening (hypophysitis/infiltrative), empty sella, apoplexy and mass effect on optic chiasm (Fleseriu JCEM 2016 ES)
  • pituitary_insultrequired
    history • used at CONTEXT
    Surgery/RT/apoplexy/Sheehan/TBI-SAH/infiltrative/genetic etiology drives screening tempo and reversibility (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
  • current_medsrequired
    medication • used at CONTEXT
    Immune-checkpoint inhibitors (anti-CTLA-4/PD-1/PD-L1), opioids and high-dose glucocorticoids cause acquired central hormone suppression / hypophysitis (Husebye Lancet 2021)
  • visual_symptomsrequired
    symptom • used at RED_FLAGS
    Bitemporal visual-field loss or new severe headache flags chiasmal compression / apoplexy needing urgent neurosurgery + ophthalmology (Fleseriu JCEM 2016 ES)

12-phase flow (12)

  1. 1FRAME
    Recognize anterior ± posterior pituitary hormone deficiency: peripheral hormone low WITH inappropriately low/normal trophic hormone, in a patient with a pituitary/hypothalamic insult; combined anterior+posterior deficiency points to stalk/hypothalamic disease (Fleseriu JCEM 2016 ES)
    inputs: cortisol, acth, free_t4, tsh
    advance: central deficiency pattern recognized and pituitary substrate plausible (Fleseriu JCEM 2016 ES)
  2. 2ENTRY
    Capture triggering finding — sellar/parasellar mass on imaging, central hormone lab pattern, pituitary-failure syndrome, post-insult presentation, or known hypopituitarism with stress/under-replacement (Fleseriu JCEM 2016 ES)
    inputs: age, sex
    advance: demographic + entry trigger documented (Fleseriu JCEM 2016 ES)
  3. 3CONTEXT
    Capture etiology: pituitary/parasellar tumor + mass effect, transsphenoidal surgery / cranial RT, apoplexy, Sheehan syndrome, lymphocytic hypophysitis (including checkpoint-inhibitor), infiltrative (sarcoidosis, hemochromatosis, Langerhans cell histiocytosis, IgG4), TBI/SAH, primary empty sella, genetic, infection; reconcile current meds (checkpoint inhibitors, opioids, supraphysiologic steroids) (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    inputs: pituitary_insult, current_meds, age, sex
    advance: etiology classified and reversible/iatrogenic contributors reconciled (Fleseriu JCEM 2016 ES)
  4. 4RED_FLAGS
    Secondary adrenal insufficiency / impending adrenal crisis (hypotension, hypoglycemia, hyponatremia), severe symptomatic hyponatremia, chiasmal compression / acute visual loss, pituitary apoplexy (thunderclap headache + ophthalmoplegia), checkpoint-inhibitor hypophysitis with hypocortisolism (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    inputs: sbp, sodium, visual_symptoms
    actions: calc.qsofa, calc.news2
    advance: red flags screened; empiric stress-dose hydrocortisone given if adrenal-crisis pattern WITHOUT waiting for cortisol/ACTH result (Fleseriu JCEM 2016 ES)
  5. 5INITIAL_WORKUP
    0800 cortisol + paired ACTH; free T4 + TSH (central rules); LH/FSH + testosterone or estradiol; prolactin; IGF-1; CMP (Na, glucose, corrected calcium); paired serum/urine osmolality if polyuria (central DI vs SIADH) (Fleseriu JCEM 2016 ES; Persani JCEM 2018)
    inputs: cortisol, acth, free_t4, tsh, sodium, prolactin
    actions: panel.hormone, panel.thyroid, panel.metabolic, workup.hypopituitarism
    advance: baseline anterior-axis panel + electrolytes sent; corrected calcium and osmolalities resulted (Fleseriu JCEM 2016 ES)
  6. 6BRANCHING_WORKUP
    Dynamic testing where basal is equivocal: insulin tolerance test (gold standard for ACTH + GH; contraindicated in seizure/IHD/elderly) or short cosyntropin/ACTH stim (caveat: may be falsely normal in recent-onset secondary AI <4–6 weeks post-insult); glucagon stim if ITT contraindicated; dedicated sellar MRI for tumor/stalk/empty sella/apoplexy/infiltrative; ferritin/ACE/IgG4 if infiltrative; never use TSH alone for central hypothyroidism (Fleseriu JCEM 2016 ES; Persani JCEM 2018; Yuen JCEM 2019 AACE/ACE GH)
    inputs: mri_pituitary, igf1, cortisol, acth
    actions: workup.pituitary_apoplexy, workup.adrenal_incidentaloma
    advance: each ambiguous axis confirmed by appropriate dynamic test; MRI and infiltrative screen resulted (Fleseriu JCEM 2016 ES)
  7. 7DIFFERENTIAL
    Phenotype etiology: tumor/parasellar mass + mass effect, surgical/RT-induced, apoplexy, Sheehan, lymphocytic / checkpoint-inhibitor hypophysitis, infiltrative (sarcoid/hemochromatosis/LCH/IgG4), TBI/SAH, empty sella, genetic, infection; distinguish secondary AI from primary AI, central from primary hypothyroidism, and central DI from SIADH/primary polydipsia (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    advance: etiologic phenotype assigned and axis-by-axis deficiency map complete (Fleseriu JCEM 2016 ES)
  8. 8RISK_STRATIFICATION
    Stratify by ACTH-axis status (overt secondary AI = highest risk), number of axes deficient, posterior-axis involvement (central DI risk in unconscious/NPO patient), mass effect / visual compromise, and intercurrent stress; qSOFA/NEWS2 triage acute decompensation (Fleseriu JCEM 2016 ES)
    inputs: sbp, sodium
    actions: calc.qsofa, calc.news2
    advance: severity tier assigned; admission vs outpatient titration decided (Fleseriu JCEM 2016 ES)
  9. 9TREATMENT
    Sequence replacement: glucocorticoid FIRST (hydrocortisone 15–20 mg/day divided, larger AM dose), THEN levothyroxine titrated to free T4 mid-reference (NEVER before glucocorticoid — accelerates cortisol clearance → adrenal crisis), then sex steroids, then GH where indicated, and desmopressin for confirmed central DI; treat acute decompensation via adrenal-crisis pathway; surgery/RT for mass effect; checkpoint-inhibitor hypophysitis usually needs only physiologic replacement (high-dose steroids reserved for mass effect/optic compromise) (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    inputs: cortisol, free_t4, sodium, sbp
    advance: glucocorticoid established BEFORE levothyroxine; remaining axes sequenced; DI replacement and mass-effect plan in flight (Fleseriu JCEM 2016 ES)
  10. 10DISPOSITION
    Admit for adrenal crisis, symptomatic severe hyponatremia, apoplexy with visual loss, or checkpoint-inhibitor hypophysitis with hypocortisolism; otherwise outpatient endocrine titration with neurosurgery referral for compressive lesions (Fleseriu JCEM 2016 ES)
    advance: admit vs outpatient decided; endocrine + neurosurgery/oncology referrals made as indicated (Fleseriu JCEM 2016 ES)
  11. 11MONITORING
    Glucocorticoid by clinical response (no reliable biomarker — avoid over-replacement); levothyroxine by free T4 (NOT TSH) at 6–8 weeks; testosterone/estradiol and symptoms; IGF-1 for GH titration; sodium and osmolality for desmopressin (avoid hyponatremia from over-treatment of DI) (Fleseriu JCEM 2016 ES; Persani JCEM 2018; Yuen JCEM 2019 AACE/ACE GH)
    inputs: free_t4, sodium, igf1
    actions: panel.hormone, panel.thyroid, panel.metabolic
    advance: each replaced axis at target on the correct (central-rule) biomarker without over-replacement (Fleseriu JCEM 2016 ES)
  12. 12FOLLOWUP
    Lifelong endocrine follow-up; stress-dosing / sick-day-rules education, emergency IM hydrocortisone kit, steroid card + MedicAlert; serial MRI for residual tumor; re-screen axes after RT (delayed hypopituitarism years later); fertility-induction referral if pregnancy desired (Fleseriu JCEM 2016 ES; Husebye Lancet 2021)
    advance: sick-day rules taught; emergency kit + steroid card issued; surveillance MRI and axis re-screening scheduled (Fleseriu JCEM 2016 ES)