Comment
for any goal would need multicentre studies enrolling
thousands of patients. The ESTIMABL15 and ESTIMABL28
trials and the HiLo trial6, on the contrary, have shown that
prospective studies are feasible in patients with thyroid
cancer and can resolve age-old, controversial issues.
I declare no competing interests.
Furio Pacini
pacini8@unisi.it
Section of Endocrinology, University of Siena, Siena, Italy
1 Mazzaferri EL, Young RL, Oertel JE, Kemmerer WT, Page CP. Papillary thyroid
carcinoma: the impact of therapy in 576 patients. Medicine (Baltimore)
1977; 56: 171–96.
2 Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical
therapy on papillary and follicular thyroid cancer. Am J Med 1994;
97: 418–28.
3 Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine
ablation in patients with low-risk thyroid cancer. N Engl J Med 2012;
366: 1663–73.
Decision making in differences of sex development/intersex
care in the USA: bridging advocacy and family-centred care
“We now know this approach [early genital surgery]
was harmful and wrong.”1 Two major US children’s
hospitals (Lurie Children’s Hospital, Chicago, IL, and
Boston Children’s Hospital, Boston, MA) announced
a suspension of some elective genital surgeries,
particularly clitoroplasty. This announcement emerged
in the context of nation-wide social and broadcast
media criticising the practice and was widely depicted
as a common-sense victory for the community of
individuals identifying as intersex. It is noteworthy
that this new policy, adopted by the two US children’s
hospitals, does not state that it is at variance with
a systematic review of outcome studies and clinical
practice guidelines.2 This discrepancy is not altogether
surprising because even the most authoritative clinical
practice guidelines do not constitute mandated
pathways of care that must be followed, but are
intended for providers to consider.
Differences of sex development (DSDs) include
a spectrum of congenital conditions in which
development of chromosomal, gonadal, or anatomical
sex is atypical.3 Concerns shared by clinicians, patients,
and their caregivers over DSD-associated features
include atypical reproductive or sex anatomy, risk of
gonadal tumours, potential need for life-long hormone
replacement, reduced or absent fertility, and their
www.thelancet.com/diabetes-endocrinology Vol 10 June 2022 381
4 Mallick U, Harmer C, Yap B, et al. Ablation with low-dose radioiodine and
thyrotropin alfa in thyroid cancer. N Engl J Med 2012; 366: 1674–85.
5 Schlumberger M, Leboulleux S, Catargi B, et al. Outcome after ablation in
patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up
results of a randomised, phase 3, equivalence trial.
Lancet Diabetes Endocrinol 2018; 6: 618–26.
6 Dehbi H-M, Mallick U, Wadsley J, Newbold K, Harmer C, Hackshaw A.
Recurrence after low-dose radioiodine ablation and recombinant human
thyroid-stimulating hormone for differentiated thyroid cancer (HiLo):
long-term results of an open-label, non-inferiority randomised controlled
trial. Lancet Diabetes Endocrinol 2019; 7: 44–51.
7 Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid
Association management guidelines for adult patients with thyroid
nodules and differentiated thyroid cancer: the American Thyroid
Association Guidelines Task Force on Thyroid Nodules and Differentiated
Thyroid Cancer. Thyroid 2016; 26: 1–133.
8 Leboulleux S, Bournaud C, Chougnet CN, et al. Thyroidectomy without
radioiodine in patients with low-risk thyroid cancer. N Engl J Med 2022;
386: 923–32.
9 Iyer NG, Morris LG, Tuttle RM, Shaha AR, Ganly I. Rising incidence of second
cancers in patients with low-risk (T1N0) thyroid cancer who receive
radioactive iodine therapy. Cancer 2011; 117: 4439–46.
collective implications for the person’s physical health
and well-being.
Controversy surrounding DSD health care currently
centres on surgical interventions on the genitals (with
consequences on appearance and function) or the
Shutterstock
gonads (with consequences on fertility) performed at an
age when the individual is unable to provide informed
consent or meaningful assent. For some activists, Published Online
early surgical procedures are tantamount to torture.4 April 21, 2022
https://doi.org/10.1016/
This view is predicated on the idea that biological sex S2213-8587(22)00115-2
is not binary5 and that these procedures constitute a
medicalisation of natural human variation.
Advocacy groups, political activism, and the building
of an intersex community has led to improved clinical
practice by drawing attention to the importance of
complete openness in educating people with DSDs
about their condition and promoting positive coping by
parents through peer support and the full integration
of psychosocial services in the model of care.3 Messages
of the movement spurred the development of several
networks (I-DSD, DSD-Life, DSDnet, Endo-ERN in Europe,
and the DSD Translational Research Network in the USA)
created to address deficiencies in diagnostic strategies,
standardisation of care, management of psychosocial
factors, and measurement of outcomes.6 Yet, current
activism has shifted its targets and methods from
 Comment
collaborating with health care to using legislative and
legal actions to achieve its objectives, including a ban on
all elective urogenital or gonadal surgery performed in
childhood.7
Why the change? There was a profound sense among
some that the medical community was not acting
quickly enough. The new era of intersex activism adopts
a human rights framework and labels elective urogenital
or gonadal surgery as medically unnecessary and a
violation of the child’s bodily autonomy. In this context,
data comparing quality of life with or without surgery
has little relevance.
The paradigm for DSD care, going back to the mid-
1950s,8 has made early urogenital surgery a standard of
care. There are accounts of terrible patient experiences
attributed to early surgery,4 as well as studies suggesting
that early surgery is compatible with favourable patient-
reported outcomes in the majority, but not all.9 These
circumstances strongly suggest that providers need
to be less prescriptive in making recommendations to
parents and instead share, in a balanced manner, the
difference between our best intentions and limitations
in predicting outcomes. Even with stronger evidence,
there will remain a gap between best care in the
aggregate and optimal decision making for the family
in front of us. Although there might be substantial
agreement in defining success, there might also be
considerable disagreement, family to family, on how to
get there. Part of the answer to this clinical conundrum
is the imperative of shared decision making. Three
essential elements define shared decision making:
providers acknowledge, and the family recognises,
that a decision is required; those involved need to
understand the best evidence regarding harms and
benefits of all treatment options, including the option
of no intervention; and the values and preferences of
patients (and those of the child’s parents) need to be
incorporated.
Should parents of young children with a DSD, in
consultation with the child’s providers, be permitted
to engage in shared decision making regarding elective
and irreversible surgical decisions? The American Medical
Association Council on Ethical and Judicial Affairs began
their rich analysis of this question with the premise that
society expects parents to make decisions in the child’s
best interests. This right and responsibility stems from
the family providing the child’s usual, often only, source
382 www.thelancet.com/diabetes-endocrinology Vol 10 June 2022
of support and care. Accordingly, the family’s needs
and interests are relevant to treatment decisions.10
The American Medical Association report recognises
a continuum of decisions: at one pole there are
decisions regarding interventions with strong evidence
of substantial benefits over potential harms; here,
providers are obliged to persuade reluctant parents to
accept the intervention. At the other pole are decisions
involving interventions for which evidence shows risk
of substantial harm without foreseeable benefit; here,
providers are responsible for dissuading caregivers from
intervening and, if unsuccessful, should decline providing
the requested intervention. Between these extremes are
interventions which providers, in good faith, may hold
diverging judgements and evidence is limited, equivocal,
or contested. If decisions regarding elective DSD-related
surgery fall in this middle category, then providers are
encouraged to “negotiate with decision makers a shared
agreement about how to understand this patient’s
medical and psychosocial interests and what plan of
care will best serve those interests in the individual’s
unique circumstances and in most cases should give
great deference to parental preferences.”10 In our opinion,
such shared agreement should acknowledge that elective
urogenital surgery in young children is considered by
some a violation of the child’s right to bodily autonomy.
Is there published evidence that the principles of
shared decision making are being applied with fidelity
in the context of DSD-related surgical decision making?
Not really, but progress is occurring. Health-care
delivery by interdisciplinary teams is replacing single-
specialty care as the standard and psychosocial services
are recognised as an integral part of DSD care by major
specialty societies. Shared decision making is predicated
on a clear understanding of its importance and
principles and high-functioning teams are more likely
to achieve success in its integration within the routine
workflow of DSD care.
Is progress in DSD research and clinical care too slow?
For sure. But progress is slowed to ensure evidence
is generalisable before it is disseminated and goes
beyond expert opinion. The formation of international
DSD networks continues to facilitate studies of the
associations between diagnosis, clinical presentation,
psychosocial factors, and both physical health and
quality of life outcomes in these individually rare
conditions. The pace of progress, however, might never

satisfy some if the only criterion by which health care
is judged is to see an end to all early elective urogenital
and gonadal surgery. There is a risk that legislatures and
courts will eventually put pressure on medical practice
to abandon some or all genital surgeries. But is this
progress? Will it apply to all urogenital modifications,
affecting both function and appearance? At this time,
we can only speculate about the life experiences and
well-being of children born with atypical genitalia who
are prevented from receiving reconstructive surgery.
How do we know what’s best (and best according to
whom) without systematically gathering data? Even
then, the importance of particular treatment outcomes
will vary according to the specifics of the child’s
condition and the family involved. For this reason, we
strongly recommend that providers of DSD health care
seek out opportunities to learn and practice the skills of
shared decision making. Blanket bans are blunt tools,
inflexible in the face of complex family situations, and
often unyielding to evidence.
DES and EV contributed equally. EV declares research funding from the National
Institutes of Health; payment for expert testimony by Nichols Kaster & Gender
Justice; and stocks and stock options from Bionano Genomics. DES declares
research funding from the National Institutes of Health; payment for expert
testimony by Estes, Ingram, Foels & Gibbs, and PA Attorneys at Law; advisory
board membership at Accord Alliance; medical and scientific advisory board
membership at CARES Foundation; membership of the American Psychological
Association (APA) Task Force on Differences of Sex Development; and co-chair of
Differences of Sex Development Special Interest Group at the Society for Pediatric
Psychology, Division 54 of the APA. DES and EV are the principal investigators of
the DSD Translational Research Network, funded by The Eunice Kennedy Shriver
National Institute of Child Health and Human Development (grant number R01
HD093450). We also would like to thank Melissa Gardner, Kathleen van Leeuwen,
Natalie Nokoff, Emmanuele Delot, Meilan Rutter, Phyllis Speiser, Erica Weidler
www.thelancet.com/diabetes-endocrinology Vol 10 June 2022 383
Comment
Baimbridge, Rama Kastury, Casey Seideman, Amanda Saltzman,
Alla Vash-Margita, and other members of the DSD Translational Research
Network for their invaluable comments.
*David E Sandberg, Eric Vilain
dsandber@med.umich.edu
Division of Pediatric Psychology, Department of Pediatrics and the
Susan B Meister Child Health Evaluation and Research Center, University of
Michigan Medical School, Ann Arbor, MI 48109, USA (DES); Center for Genetic
Medicine Research, Children’s National Hospital, Washington, DC, USA (EV);
Department of Genomics and Precision Medicine, George Washington
University, Washington, DC, USA (EV); and International Research Laboratory
IRL2006 Epigenetics, Data, Politics, Centre National de la Recherche Scientifique,
Washington, DC, USA (EV).
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Children’s and Our Sex Development Clinic. 2020. https://www.
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development-clinic/ (accessed April 1, 2022).
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to steroid 21-hydroxylase deficiency: an Endocrine Society clinical
practice guideline. J Clin Endocrinol Metab 2018; 103: 4043–88.
3 Lee PA, Nordenstrom A, Houk CP, et al. Global disorders of sex
development update since 2006: perceptions, approach and care.
Horm Res Paediatr 2016; 85: 158–80.
4 Human Rights Watch. “I Want to Be Like Nature Made Me.” Medically
unnecessary surgeries on intersex children in the US. 2017. https://www.
hrw.org/sites/default/files/report_pdf/lgbtintersex0717_web_0.pdf
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system/files/2019-12/i18-ceja-report-3.pdf (accessed April 1, 2022).